Pain Pharmacology: What to Know In A Clinical Approach

Explore the latest strategies in pain pharmacology in a clinical approach to enhance patient care and treatment outcomes.

Abstract

Welcome to our educational post on the multifaceted world of pain management. As Dr. Alex Jimenez, DC, APRN, FNP-BC, CFMP, IFMCP, ATN, CCST, I am honored to guide you through a comprehensive exploration of modern pain relief strategies, grounded in the latest evidence-based research. This article delves into the physiological mechanisms of pain, beginning at the peripheral source of injury and tracing the complex signaling pathways to the central nervous system. We will closely examine the science behind various therapeutic agents, starting with often-underestimated topical treatments like diclofenac, lidocaine, and capsaicin, and explain why they are a logical and effective first-line defense. We will then transition to a deep dive into neuropathic agents, specifically anticonvulsants like gabapentin and pregabalin, which I refer to as “membrane stabilizers,” as well as certain classes of antidepressants, explaining their independent analgesic mechanisms. I will demystify how these medications work at a cellular level, discuss their appropriate use, and highlight crucial clinical considerations, including recent findings on potential long-term risks.

Furthermore, this post will navigate the complexities of opioids, benzodiazepines, and muscle relaxants, emphasizing safe prescribing, risk mitigation, and the importance of avoiding dangerous co-prescriptions. We will also explore emerging and innovative therapies, such as low-dose naltrexone (LDN) for neuroimmune modulation and the new non-opioid analgesic, suzetrigine. Throughout this discussion, I will emphasize the importance of our unique, integrative care model at Injury Medical Clinic. This model combines my expertise in chiropractic and functional medicine with the invaluable medical oversight of our Medical Director, Dr. Maria Guadalupe Cardenas, MD, a board-certified internist with over four decades of experience. Together, we provide a holistic, patient-centered journey toward healing, integrating chiropractic adjustments, rehabilitative therapies, and advanced medical protocols to address pain from every possible angle.

Our Integrative Care Philosophy: A Collaboration for Comprehensive Healing

At Injury Medical Clinic PA, also known as Mission Plaza Injury Medical Clinic, our approach to patient care is built on collaboration and integration. My practice is a multidisciplinary environment where different fields of medicine converge to provide the most comprehensive treatment possible. I am Dr. Alex Jimenez, and my background spans chiropractic (DC), advanced practice nursing (APRN, FNP-BC), and certified functional medicine (CFMP, IFMCP). This allows me to view health and injury through multiple lenses, but true integrative care thrives on collaboration.

Crucial to our model is the partnership with Dr. Maria Guadalupe Cardenas, MD. Dr. Cardenas is a highly respected, board-certified internist with an impressive career spanning over 40 years. She serves as our Medical Director and Collaborative Physician, providing essential medical oversight for our patients. Her NPI is #1164426749, and her Texas MD License is #J2933. This type of multidisciplinary setup, where a medical doctor provides direction alongside a chiropractor, is a hallmark of progressive integrative and injury care clinics.

Our team synergizes our expertise to offer a full spectrum of services:

• Medical Oversight (Dr. Cardenas): Provides diagnostic clarity, manages complex medical conditions, manages prescriptions where necessary, and oversees prescriptive and advanced medical interventions, bringing immense medical knowledge and diagnostic acumen to our team.
• Chiropractic & Functional Medicine (Dr. Jimenez): Focuses on biomechanical alignment, the musculoskeletal system, nervous system function, musculoskeletal rehabilitation, restoring functional movement patterns, and addressing the root causes of disease through functional medicine principles.
• Integrated Services: Together, we manage personal injury cases, post-surgical rehabilitation, and chronic pain conditions, utilizing a toolkit that includes chiropractic adjustments, physical therapy, nutritional counseling, and, when appropriate, pharmacological support.

When a patient walks through our doors, they are not just seeing a chiropractor or a medical doctor; they are accessing a cohesive team dedicated to their recovery. This collaborative model ensures that every patient receives a treatment plan that is not only effective but also safe, holistic, and tailored to their unique physiological needs. This model is particularly vital in managing complex conditions like chronic pain, where the solution is rarely a single intervention but a symphony of coordinated therapies. Integrative chiropractic care, in this context, is not a standalone therapy but a vital component of a larger strategy. Spinal adjustments, for example, can improve nervous system communication and reduce musculoskeletal stress, which complements the action of the pharmacological agents we will discuss, creating a powerful, synergistic effect for pain relief and healing.

Starting at the Source: The Power of Topical Pain Relief

I often find that topical agents are an overlooked yet incredibly powerful tool in our pain management arsenal. When I consult with patients, one of the first things I do is take them on a journey to understand how pain actually works.It’s not just a single event; it’s a complex, multi-step process. By explaining this, patients can better appreciate why our treatment strategies are designed the way they are.

I tell them, “Think about what happens when you injure yourself—say, you accidentally slam your hand in a door or get a burn. The pain doesn’t just magically appear in your brain. It starts right there, at the site of the injury, in what we call the periphery.” This initial step is called transduction.

At the moment of injury, your body releases a cocktail of chemicals directly into the tissue. These chemicals trigger a cascade of events that creates an electrical signal. This signal then travels along your nerves from the periphery to your spinal cord—a step known as transmission. From the spinal cord, the signal is relayed up to the brain, where it is processed and perceived as the sensation we call pain.

The beauty of understanding this pathway is that it reveals multiple opportunities for us to intervene. It simply makes sense to start our intervention at the very beginning of the process—at the source of the pain signal in the periphery. This is precisely where topical agents do their work.

Unpacking the “Chemical Soup” of Peripheral Pain Activation

To truly grasp why topical treatments are so effective, we need to look closer at what happens at the cellular level during an injury. I often use a simple drawing to illustrate this for my patients, as I find visual aids can make these complex concepts much more accessible.

Imagine a nail piercing the skin. This tissue damage immediately causes the release of several key inflammatory and pain-mediating substances:

• Prostaglandins: These are lipids that are synthesized right at the site of tissue damage. They don’t directly cause pain, but they are powerful sensitizers. They lower the activation threshold of the peripheral nerve endings, called nociceptors, making them much more responsive to other pain-producing stimuli. This is a crucial concept. Think of prostaglandins as turning up the volume on the nerve’s “pain microphone.”
• Histamine: Released from specialized immune cells called mast cells, histamine is well-known for causing itching and swelling. It also contributes to the sensitization of nociceptors, adding to the overall inflammatory response.
• Bradykinin: This is a potent pain-producing peptide. Once prostaglandins have sensitized the nociceptors, bradykinin can directly activate them, causing a strong, burning pain sensation.
• Serotonin: Released from platelets, serotonin also contributes to the inflammatory soup and enhances pain signaling.
• Substance P and Calcitonin Gene-Related Peptide (CGRP): These are neuropeptides released from the nociceptor endings themselves. They play a dual role: they contribute to neurogenic inflammation by causing vasodilation (swelling and redness), and they further amplify the pain signal being sent back to the spinal cord.

This entire “chemical soup” works together to open ion channels on the nociceptors, generating that initial electrical impulse that travels to the brain. By applying a topical agent directly to the affected area, we can interfere with these very chemicals, effectively stopping the pain signal before it even gets a strong start.

The Hidden Risks of Common Pain Medications

As clinicians, we are constantly weighing the benefits of a treatment against its potential risks. This is especially true when we consider medications for chronic pain. Even drugs we have come to view as relatively “safe,” like non-steroidal anti-inflammatory drugs (NSAIDs), carry a significant burden of risk that we must communicate to our patients.

Research has consistently shown that long-term or high-dose use of NSAIDs is linked to a host of serious health issues. These aren’t minor side effects; they are major systemic problems that can have life-altering consequences.

• Cardiovascular Risks: We now have strong evidence linking NSAID use to an increased risk of heart failure, myocardial infarction (heart attack), and peripheral vascular disease. The mechanisms are complex, involving effects on blood pressure, renal function, and prostaglandin synthesis, all of which can strain the cardiovascular system.
• Gastrointestinal Damage: The classic risk of stomach ulcers and bleeding is well-known, but the damage can extend throughout the entire GI tract.
• Kidney Damage: NSAIDs can impair renal blood flow, leading to acute kidney injury or worsening chronic kidney disease, a particularly concerning issue for our aging population and those with comorbidities like diabetes and hypertension.

This evidence underscores a critical point in modern pain management: there is no single “magic bullet.” The idea of relying heavily on one class of medication is becoming increasingly outdated and unsafe. Instead, the paradigm is shifting towards a multimodal approach, where we use a little of this and a little of that. This strategy allows us to leverage different mechanisms of action while keeping the dose of any single agent low, thereby minimizing the risk profile. It is about being smarter, more strategic, and more holistic in our prescribing and treatment planning.

Diclofenac Gel (Voltaren): A Potent Anti-Inflammatory Without the Systemic Risks

One of the most effective and widely used topical agents is diclofenac gel, commonly known by the brand name Voltaren. It is also available in patch form (Flector) and as a solution (Pennsaid). Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), and its mechanism of action is beautifully simple and direct.

• How it Works: Diclofenac works by blocking the cyclooxygenase (COX) enzymes, which are responsible for producing prostaglandins. By inhibiting prostaglandin synthesis right at the site of injury, it prevents that initial sensitization of the nociceptors. Without the sensitizing effect of prostaglandins, other pain-producing substances like bradykinin have a much harder time activating the nerve. We are essentially cutting off a key instigator of the pain cascade.
• Clinical Efficacy: What I find most compelling, and what the research supports, is that the efficacy of topical NSAIDs like diclofenac is often comparable to that of oral NSAIDs when used consistently for localized musculoskeletal pain, such as in osteoarthritis of the hands or knees. One study demonstrated that after a week of consistent, daily application, topical diclofenac provided as much pain relief as an oral NSAID.
• Superior Safety Profile: This is the most significant advantage. By applying the medication topically, we deliver a high concentration of the active drug directly to the target tissue while achieving very low systemic (blood) concentrations. This dramatically reduces the risk of the well-known side effects associated with oral NSAIDs, such as gastrointestinal bleeding, ulcers, and cardiovascular events (heart attack and stroke). This makes it an excellent choice for our elderly patients or those with pre-existing GI or cardiovascular conditions. In fact, the American College of Rheumatology strongly recommends topical NSAIDs for patients over 75 with knee or hand osteoarthritis.

I often recommend diclofenac gel to my patients with osteoarthritis, especially those affecting the hands. My patients who are avid knitters, for example, have found immense relief by applying the gel to their finger joints, allowing them to continue their beloved hobby with significantly less pain. I advise them to apply it consistently, making it part of their daily routine. A helpful tip is to keep a tube in the bathroom and another by the kitchen sink as a reminder. The gel (1%) is typically applied two to four times a day. It’s also important for them to know that the active ingredient is absorbed within about 20 minutes, so if they wash their hands after that time, they won’t lose the therapeutic benefit.

The Flector patch (diclofenac 1.3%) is specifically indicated for acute pain from minor strains, sprains, and contusions. This is a fantastic option for someone who comes into my clinic with acute low back pain after “throwing their back out.” The patch provides a steady, controlled release of the medication over 12 hours, offering sustained relief directly at the site of the muscle spasm or ligamentous sprain.

Topical Anesthetics: Silencing the Signal with Lidocaine

Another cornerstone of topical therapy is the use of local anesthetics, with the lidocaine patch being the most common example. While diclofenac targets the inflammatory chemicals, lidocaine works on the electrical part of the pain signal itself.

• Mechanism of Action: Pain signals travel along nerves as electrical impulses, which are generated by the rapid movement of ions—particularly sodium ions—across the nerve cell membrane. Nociceptors have specialized voltage-gated sodium channels that open and close to propagate this signal. Lidocaine works by physically blocking these sodium channels. When the channels are blocked, sodium ions cannot rush into the nerve cell, and the electrical impulse cannot be generated or transmitted. It effectively numbs the nerve, preventing it from sending the pain message to the spinal cord.
• Impressive Results in Neuropathic Pain: Lidocaine patches have shown remarkable efficacy, particularly in cases of neuropathic pain like postherpetic neuralgia (PHN). This persistent, often excruciating nerve pain can follow a shingles outbreak. A landmark study on PHN patients using the 5% lidocaine patch (Lidoderm) found a 65% improvement in pain scores and a 77% improvement in quality of life within the first week of treatment. This is a game-changer for these patients. The pain of PHN can be so severe that the light touch of clothing becomes unbearable (a phenomenon called allodynia). The inability to wear a bra, a belt, or even sleep comfortably can be debilitating. A lidocaine patch can provide a protective barrier while delivering targeted pain relief.
• Safety and Application: The patches are typically worn for 12 hours on, followed by 12 hours off. This “off” period is important to prevent skin irritation and allow the skin to recover. Patients often worry about toxicity, but studies have shown that even when multiple patches are applied to the body, the systemic absorption of lidocaine is extremely low and does not approach toxic levels. This makes it a very safe long-term option.

In my practice, integrating lidocaine patches with chiropractic care for a condition like PHN affecting the thoracic spine is highly effective. Gentle chiropractic adjustments can help improve spinal mobility and reduce nerve root irritation, while the lidocaine patch works peripherally to block the pain signals emanating from the affected dermatome. This dual approach addresses both the central and peripheral components of the pain.

Capsaicin: Depleting the Pain Messengers

Capsaicin, the compound that gives chili peppers their heat, is a fascinating and potent topical analgesic. It works through a completely different mechanism than NSAIDs or local anesthetics.

• A Unique Mechanism: Capsaicin targets a specific receptor on nociceptors called the Transient Receptor Potential Vanilloid 1 (TRPV1). This receptor is a heat-activated calcium channel. When you apply capsaicin, it binds to and activates these TRPV1 receptors, causing a flood of calcium ions into the nerve cell. This initially causes a sensation of burning and warmth, as the receptor is “tricked” into thinking it’s being exposed to heat.
• Depletion and Desensitization: With repeated application, this constant activation has a profound effect. The nerve endings become overwhelmed and are depleted of Substance P, a key neuropeptide involved in transmitting pain signals and promoting inflammation. Furthermore, prolonged activation eventually leads to desensitization and even temporary, reversible degeneration of the nerve endings themselves. In essence, capsaicin first excites the nerve and then exhausts it into silence.
• Formulations and Uses: Capsaicin is available in low-concentration over-the-counter creams and lotions (e.g., 0.025% to 0.1%). These need to be applied multiple times a day, consistently, for the desensitizing effect to build up. For more severe neuropathic pain, such as diabetic peripheral neuropathy and postherpetic neuralgia, there is a high-concentration prescription patch called Qutenza (8% capsaicin). This patch is applied in-office for 30 to 60 minutes, and the pain relief can last for up to three months from a single application. The procedure requires pre-treatment of the area with a local anesthetic due to the intense initial burning sensation. While getting insurance approval for Qutenza can be a challenge, for patients who respond, the results can be life-changing. I have seen patients experience significant improvement after two or three applications, spaced three months apart.

The common thread among all these topical agents is that they allow us to be highly specific. We can target prostaglandins with diclofenac, sodium channels with lidocaine, or TRPV1 receptors with capsaicin, all while minimizing systemic side effects. This is precision medicine at its best.

Off-Label and Compounded Topicals

While harder to get approved by insurance these days, compounded topical creams can be a valuable option for patients with complex conditions who have failed other therapies. These creams can combine multiple agents into a single formulation. For example, for patients with Complex Regional Pain Syndrome (CRPS), a condition involving dysfunction of the autonomic nervous system, we sometimes use a compounded clonidine gel. Clonidine is an alpha-2 adrenergic agonist that can help modulate norepinephrine activity at the peripheral nerve endings, reducing the burning pain and autonomic changes associated with CRPS.

Another important compounded preparation is “Magic Mouthwash.” There is no single standardized formula, but it is a lifesaver for patients suffering from painful oral mucositis due to chemotherapy or radiation for head and neck cancers, or for conditions like burning mouth syndrome. A typical formulation might include:

• A local anesthetic (like lidocaine) to numb the pain.
• An antacid (like Maalox or Mylanta) to help the solution coat and adhere to the oral mucosa.
• An antihistamine (like diphenhydramine) for its mild anesthetic and anti-inflammatory properties.
• Sometimes, an antifungal (like nystatin) or a corticosteroid may be added if indicated.

This customized approach provides immense relief and allows patients to eat, drink, and maintain their nutrition during difficult treatments.

Calming the Storm: Neuropathic Agents as Nerve Membrane Stabilizers

Now, let’s move from the periphery up the pain pathway and discuss a class of medications known as neuropathic agents. It’s important to clarify that this term refers to the medication’s mechanism of action, not necessarily the type of pain it treats. While these drugs are mainstays for “nerve pain”—the burning, zinging, shooting pain that often follows a nerve distribution—their stabilizing effects can be beneficial for other types of chronic pain as well.

Anticonvulsants in Pain Management: Separating Evidence from Hope

For many years, anticonvulsant medications have been a cornerstone of neuropathic pain treatment. The theory is that by calming hyperexcitable nerve signals, we can reduce pain. While this holds for some agents, it is crucial to be guided by robust clinical evidence rather than assumption.

The primary category of neuropathic agents we use is the anticonvulsants, specifically gabapentin and pregabalin. To help my patients understand how these medications work, I use the analogy of an “embrane stabilizer.” This concept is intuitive and powerfully descriptive.

Imagine a nerve that has been injured or is chronically irritated. It becomes hyperexcitable, like a frayed electrical wire that sparks erratically. The nerve cell membrane is in a constant state of agitation, almost “quivering.” It’s on a hair-trigger, firing off pain signals with little to no provocation. This is the cellular basis of neuropathic pain.

The goal of a membrane stabilizer is to calm this hyperexcitable state. These medications don’t just block a pain signal like an opioid; they work therapeutically to restore the nerve to a more normal, less reactive state. They “stabilize” the shaky membrane, making it less likely to fire spontaneously.

The Gabapentinoids: Gabapentin and Pregabalin

When we look at the body of research, two medications in this class stand out with the best evidence for efficacy in neuropathic pain:

• Gabapentin (Neurontin)
• Pregabalin (Lyrica)

These are our go-to agents for conditions like postherpetic neuralgia (shingles pain), painful diabetic neuropathy, and radicular pain (sciatica).

Gabapentin (Neurontin): The Workhorse of Membrane Stabilization

Gabapentin is one of the most prescribed medications for neuropathic pain, and for good reason. However, its effective use requires a nuanced understanding of its pharmacology and a patient, methodical approach to dosing.

• Mechanism of Action: Despite its name, gabapentin does not directly act on GABA receptors. Its primary mechanism involves binding to a specific subunit (the alpha-2-delta subunit) of voltage-gated calcium channels on presynaptic nerve terminals. In states of nerve injury, these channels are upregulated, leading to an influx of calcium and the release of excitatory neurotransmitters like glutamate and substance P. By binding to this subunit, gabapentinoids effectively turn down the volume of this hyperexcitable signaling, thereby reducing the perception of pain.

• Let me break down what this means in the context of our pain pathway. When a pain signal arrives at the end of one nerve cell (the presynaptic terminal), it triggers the opening of these calcium channels. Calcium ions rush into the cell, which is the critical step that causes the release of excitatory neurotransmitters (like glutamate and Substance P) into the synapse. These neurotransmitters then travel across the gap and activate the next nerve cell in the chain.
• Gabapentin “gets in the way.” By binding to the alpha-2-delta subunit, it reduces the influx of calcium into the nerve terminal. With less calcium coming in, there is a decreased release of these excitatory neurotransmitters. The “go” signal being sent to the next nerve is weakened. I explain it to patients like this: “This medication slows down how fast the aggravated nerve can play ‘tag’ with the next nerve in line. It gives the nerve a chance to calm down, to stop quivering, and to act more like a normal, healthy nerve.”

• Newer Findings: Research on gabapentin is ongoing, and we are constantly learning more. Recent studies suggest it may also affect glial cells, which are support cells in the nervous system that are now understood to play a major role in amplifying and sustaining chronic pain states through inflammatory processes. Gabapentin may help modulate this glial activation. Interestingly, it has also been shown to increase total serotonin levels in the brain, even without directly acting on the serotonergic system, which becomes relevant when we consider the risk of Serotonin Syndrome.
• Titration is Key: Start Low, Go Slow: This is perhaps the most critical principle in using gabapentin. If I could have every clinician take one thing away about this drug, it would be this. We must start with a very low dose (e.g., 100 mg at bedtime) and increase it very slowly (e.g., every 3-7 days). There are two main reasons for this:

1. To Avoid Side Effects: The most common side effects are drowsiness, dizziness, and mental fog. If we start at a high dose, the patient will likely feel terrible and immediately decide, “This drug is not for me.” We lose a valuable therapeutic option forever. By going slowly, we allow the body to acclimate.
2. To Find the “Sweet Spot”: We want to find the lowest effective dose for each patient. If we titrate up too aggressively, we might overshoot the optimal dose and end up giving them more medication than they need, which only increases the risk of side effects without providing additional benefit.

1. Clinical Pearls and Precautions:

• Indications: It’s important to know that gabapentin is officially FDA-indicated only for postherpetic neuralgia. Its widespread use for diabetic neuropathy, fibromyalgia, and other chronic pain states is technically off-label, though strongly supported by clinical evidence and guidelines.
• Bioavailability: This is a fascinating and often overlooked quirk of gabapentin. As the dose increases, its absolute bioavailability decreases. At a dose of 900 mg/day, about 60% of the drug is absorbed. As you go higher, to 3600 mg/day, the absorption can drop to as low as 35%. This is because the gut transport system that absorbs gabapentin becomes saturated. This means that at very high doses, you are giving the patient more drug, but a smaller percentage of it is actually getting into their system. This reinforces the idea that finding the lowest effective dose is paramount.
• Central Sleep Apnea: Gabapentin has been associated with medication-induced central sleep apnea. This is an important consideration for our patients who already have sleep apnea or are at risk.
• DRESS Syndrome: A rare but very serious adverse reaction is Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) syndrome. This is a severe, multi-organ hypersensitivity reaction that can manifest with fever, rash, and internal organ involvement. It is crucial to be aware of this, as early recognition is key. I once had a patient report developing a fever and feeling terrible after starting gabapentin. At the time, I admit I was skeptical, but I now know this can be a legitimate and dangerous reaction.

The extended-release formulations, Gralise (taken once daily with the evening meal) and Horizant (a prodrug, gabapentin enacarbil), offer smoother blood levels and can sometimes be better tolerated. However, their use is often limited by insurance coverage to their specific FDA indications (PHN for Gralise; restless legs syndrome and PHN for Horizant).

Pregabalin (Lyrica): A More Potent and Predictable Stabilizer

Pregabalin is a close cousin of gabapentin. It is often referred to as gabapentin’s “successor.”

• Mechanism of Action: Pregabalin works in the same way as gabapentin, by binding to the alpha-2-delta subunit of voltage-gated calcium channels to reduce the release of excitatory neurotransmitters. However, it has a higher binding affinity for this site, making it more potent than gabapentin.
• Pharmacokinetic Advantages: The key difference lies in its pharmacokinetics. Unlike gabapentin, pregabalin has linear and predictable absorption. This means that as you increase the dose, the amount absorbed into the bloodstream increases proportionally. This makes dosing more straightforward. It also reaches a steady state in the blood much faster, within 48 to 72 hours.
• Dosing and Titration: This faster time to steady state allows for a slightly quicker titration schedule than gabapentin. We might start a patient on 25 mg or 50 mg twice a day and increase the dose every 2-3 days as tolerated. The maximum daily dose is 600 mg, typically divided into two or three doses. However, clinical experience and studies have shown that for many patients, the therapeutic “ceiling” is around 450 mg per day. Above this dose, the increase in side effects (dizziness, somnolence, peripheral edema) often outweighs any additional pain relief. That said, some individuals do find benefit at the 600 mg dose.
• FDA Indications: Pregabalin has a broader range of FDA-approved indications, including diabetic peripheral neuropathy, postherpetic neuralgia, fibromyalgia, and neuropathic pain associated with spinal cord injury.

Other Anticonvulsants: A Word of Caution

It is just as important to know which medications do not have evidence for a particular indication. In the realm of chronic pain, two commonly misused anticonvulsants are:

• Lamotrigine (Lamictal): Despite its use in other neurological and psychiatric conditions, lamotrigine has zero evidence for efficacy in treating chronic pain. The studies have been done, and they have consistently failed to show a benefit over placebo.
• Topiramate (Topamax): This medication’s only established indication in the pain world is for migraine prophylaxis. Using it for other neuropathic pain states like shingles or complex regional pain syndrome (CRPS) is an off-label application that is not supported by scientific evidence. These conditions require different therapeutic strategies.

Our commitment to evidence-based practice means we must be disciplined in our choices, reserving medications for the conditions in which they have been proven to work. This prevents patients from enduring potential side effects from a drug that was unlikely to help them in the first place.

A New and Crucial Consideration: Cardiovascular Risk

A very important study published in 2025 has changed how we think about the long-term safety of these drugs. The study, which looked at a large cohort of patients, found a significantly increased risk of five-year adverse cardiovascular events (like heart attack and stroke) in patients with diabetic neuropathy taking gabapentinoids (gabapentin or pregabalin). This finding was then duplicated in a second study of patients with fibromyalgia.

This is new and critically important information. It does not mean we should stop using these effective medications. However, it does mean we must be more judicious. It underscores the need for a thorough discussion with our patients about the potential long-term risks versus the benefits, especially in those with pre-existing cardiovascular risk factors. It also reinforces the value of our integrative approach. By incorporating non-pharmacological treatments like chiropractic care, which improves biomechanics and nervous system function, and functional medicine, which can address underlying metabolic issues like insulin resistance that contribute to both neuropathy and cardiovascular disease, we can potentially reduce the patient’s reliance on high doses of these medications and mitigate their overall risk profile.

In my clinical observations, patients who engage in a comprehensive program that includes regular chiropractic adjustments, targeted rehabilitative exercises, and anti-inflammatory nutritional strategies often require lower doses of neuropathic agents to achieve pain control. The adjustments help to decompress nerve roots and improve signaling, while the medications work at the cellular level to stabilize the nerves. This synergy is the essence of true integrative pain management. Our collaboration with Dr. Cardenas ensures that this entire process is managed under a safe and comprehensive medical umbrella, allowing us to navigate these complex treatment decisions with confidence and care.

The Role of Antidepressants in Pain Management: Beyond the Mood

One of the most common and challenging conversations I have with patients involves the recommendation to use an antidepressant for their pain. Almost invariably, the patient’s initial reaction is to feel misunderstood or judged. They say things like:

• “Are you saying the pain is all in my head?”
• “Do you think I’m just stressed out or depressed?”
• “Are you implying I’m making this up?”

This is a completely understandable reaction, and it is our job as clinicians to address this misconception with empathy and proactive, clear education. The truth is, certain antidepressants are powerful, legitimate pain medications in their own right, and their analgesic effects are entirely independent of their effects on mood.

Decoding the Mechanism: The Descending Pain Pathway

To understand how antidepressants work for pain, we need to revisit the journey of a pain signal. When you experience an injury, the signal starts in the periphery (e.g., your skin, a muscle), travels up the nerves to the spinal cord, and then ascends to the brain. In the brain, the signal is processed in various regions, and only then do you consciously experience the sensation of “pain.”

But the story doesn’t end there. The brain is not a passive recipient of these signals; it has a sophisticated, built-in system to modulate or “turn down” incoming pain signals. This is known as the descending inhibitory pathway. Think of it as the brain’s own pain-relief system. This pathway originates in areas of the brainstem and projects down the spinal cord, releasing neurotransmitters that inhibit the transmission of pain signals from the periphery.

Two of the most important neurotransmitters in this descending pathway are serotonin and, even more critically for pain, norepinephrine. A dysfunction or depletion of this descending inhibitory system characterizes many types of chronic pain. The pain signals are essentially coming in too loud and clear, without the brain’s natural “muffling” effect.

This is where certain antidepressants, particularly the Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) and Tricyclic Antidepressants (TCAs), come into play. By increasing the available levels of serotonin and norepinephrine in the synaptic clefts of this descending pathway, these medications effectively boost the brain’s own ability to block pain signals. They are not treating depression; they are restoring a dysfunctional pain-modulating circuit.

Key Talking Points for Patients

When I introduce this concept, I make sure to emphasize several key points to build trust and ensure adherence:

• A Real Pain Medication: “We are using this medication because it has been proven in rigorous scientific studies to treat physical pain, even in people who have no signs of depression or anxiety.”
• Studied in Non-Depressed Patients: “The major clinical trials for these drugs in pain specifically excluded people with mood disorders to make sure the pain-relieving effect was real and not just a side effect of improved mood.”
• Non-Addictive: “Unlike opioids, these medications are not addictive. This is a safe, long-term strategy for managing your pain.”
• Convenient Dosing: “It is typically a simple, once-a-day dose.”

Timing the explanation of this mechanism empowers the patient. It transforms their perception from “My doctor thinks I’m crazy” to “My doctor understands the complex neuroscience of my pain and is using a targeted tool to help my brain fight it.”

Addressing Patient Fears: The Black Box Warning and Serotonin Syndrome

Effective communication also means directly addressing the fears patients may have, which they often discover through a quick internet search or from the pharmacy printout. Two of the biggest concerns with antidepressants are the “black box warning” about suicide risk and the dreaded “serotonin syndrome.”

Navigating the Black Box Warning

In 2004, the FDA issued a black box warning—the most serious type of warning—for all antidepressant medications. This was in response to data showing an increased risk of suicidal thoughts and behaviors in children and adolescents being treated with SSRIs. This warning was then applied as a blanket statement across all antidepressants for all age groups.

While any risk of suicide is profoundly serious and must be taken into account, we need to provide our patients with the full context. Panicking and avoiding these helpful medications altogether is often not the right answer. Here are the crucial talking points I use to have this important but quick conversation:

• The Original Finding: The risk was identified specifically in children and adolescents.
• No Increased Risk in Adults: In clinical trials, patients above the age of 24 showed no increased risk of suicidality when taking antidepressants.
• The Highest-Risk Group: The group with the most significant risk was young men aged 18 to 25. The prevailing theory is that in this group, the medication can sometimes increase energy and motivation before it improves mood. This can create a dangerous window where an individual who was previously too lethargic to act on suicidal thoughts suddenly has the energy to do so. This is why close monitoring is essential in the initial weeks of treatment for this demographic.
• A Protective Effect in Older Adults: Perhaps the most reassuring piece of data is that in adults aged 65 and over, antidepressants have been shown to have a protective effect, actually reducing the risk of suicidality compared to placebo.

I can explain all of this to a patient in less than 90 seconds. It shows them that I am aware of the risks, take them seriously, and have also analyzed the data and can contextualize it for their specific situation. This transparency builds immense trust and prevents them from coming back to my office, panicked that I prescribed a medication “that’s going to make them kill themselves.”

Understanding Serotonin Syndrome

Serotonin syndrome is another topic that generates a lot of fear, both among patients and clinicians. Patients will come in self-diagnosing, or a pharmacist will call, concerned that a patient is on multiple “serotonergic” drugs. While we absolutely need to be aware of this potential adverse event, especially with the proliferation of psychotropic medications, it’s important to recognize that true serotonin syndrome is rare.

Key Characteristics of Serotonin Syndrome:

• Rapid Onset: It does not develop insidiously over months. In about 30% of cases, symptoms appear within one hour of taking a new drug or an increased dose, and in 60% of cases, they appear within six hours.
• Autonomic Hyperactivity: The classic presentation is a triad of symptoms involving altered mental status (agitation, confusion), autonomic instability (fever, sweating, tachycardia), and neuromuscular hyperactivity.

The diagnostic challenge is that many of these symptoms—like sweating and agitation—can look like many of my patients on any given day, or they could be a reaction to a different medication. Fortunately, we are not left to guess.

The Hunter Criteria: A Definitive Diagnostic Tool

To standardize the diagnosis and avoid overdiagnosis, we use the Hunter Serotonin Toxicity Criteria. This is a straightforward, evidence-based diagnostic tool. To meet the criteria, a patient must:

1. Be taking a known serotonergic agent.
2. Exhibit one of the following specific combinations of signs:

• Spontaneous clonus (involuntary, rhythmic muscle contractions)
• Inducible clonus PLUS agitation or diaphoresis (sweating)
• Ocular clonus (rhythmic eye movements) PLUS agitation or diaphoresis
• Tremor PLUS hyperreflexia (overactive reflexes)
• Hypertonia (increased muscle tone) PLUS a temperature above 38°C (100.4°F) PLUS ocular or inducible clonus

What you will notice is that clonus is the star of the show here. It is a key, objective neurological sign that we can test for at the bedside in about 30 seconds by sharply dorsiflexing the patient’s ankle. Its presence is a major red flag. Similarly, testing reflexes is a standard part of our physical exam. Knowing these criteria empowers us to differentiate true serotonin syndrome from non-specific anxiety or other side effects, allowing for more rational clinical decision-making. If a patient does meet the criteria, the primary treatment is to discontinue the offending agents and provide supportive care.

Balancing Body and Metabolism- Video

Specific Antidepressants for Pain: Choosing the Right Tool

Now that we have established the “why” behind using antidepressants for pain, let’s look at the “which.”

Duloxetine (Cymbalta): The SNRI Powerhouse

Duloxetine is a serotonin-norepinephrine reuptake inhibitor (SNRI) and is arguably our most well-studied and effective antidepressant for a variety of chronic pain states. It carries FDA indications for:

• Fibromyalgia
• Painful Diabetic Neuropathy
• Chronic Musculoskeletal Pain

It is this last indication—chronic musculoskeletal pain—that I want to highlight because it is truly impressive and expands our treatment possibilities. When we think of “nerve pain,” we typically think of shooting, burning, or tingling pain. We don’t usually put chronic low back pain or osteoarthritis of the knee in that category. Yet, research has shown that duloxetine can significantly improve both pain and function in these conditions.

One landmark study demonstrated that duloxetine led to statistically significant improvements in pain and function in patients with osteoarthritis (OA) of the knee at just four weeks. This is a game-changer. Why? Because the patients who suffer most from OA are often older and have multiple comorbidities (heart disease, kidney issues, hypertension) that make long-term use of NSAIDs dangerous. Duloxetine offers a completely different, and often safer, mechanism of action. It can be used alongside an anti-inflammatory for a synergistic effect or as a standalone therapy in patients who cannot tolerate NSAIDs.

Dosing and Clinical Pearls:

• Efficacy: The general expectation we set for patients is that about 50% of people will experience about 50% improvement in their pain.
• Target Dose: The standard target dose for pain is 60 mg once daily.
• Starting Dose: To minimize side effects, particularly nausea, we always start with a 30 mg dose for the first week before increasing to 60 mg. Nausea is the most common reason for discontinuation, so being proactive is key. I will often write a contingent prescription for an anti-nausea medication like ondansetron (Zofran) to help patients get through that initial adjustment period. We have a limited number of effective tools, and I do not want to lose a potentially life-changing medication because of a transient, manageable side effect.

The evidence for duloxetine in chronic musculoskeletal pain means we can—and should—consider it for conditions like chronic low back pain and even OA of the shoulder, where the underlying mechanism of central sensitization is similar.

Other SNRIs: Milnacipran and Venlafaxine

Two other SNRIs are sometimes mentioned in the context of pain, but their roles are more limited.

• Milnacipran (Savella): This SNRI is unique in that it is only FDA-indicated for fibromyalgia. It is also only available as a brand-name drug, which can create access issues and prevent off-label use. Of all the SNRIs, milnacipran has the highest affinity for norepinephrine relative to serotonin. This can be a double-edged sword. While norepinephrine is key for pain modulation, it can also cause more side effects like agitation, tremor, and increased heart rate, making it feel too “speedy ” for some patients. Interestingly, the clinical trials for Savella defined success as a 30% reduction in pain from baseline. The fact that this was considered a meaningful outcome speaks volumes about the profound suffering experienced by people with fibromyalgia.
• Venlafaxine (Effexor): While venlafaxine is also an SNRI, the data supporting its use for pain is much weaker than for duloxetine. There is some evidence for its use in painful diabetic neuropathy, but it would never be my first-line choice. It is a medication to be aware of, but not one to reach for initially.

Tricyclic Antidepressants (TCAs): The Old School Option

Long before the SNRIs, we had the Tricyclic Antidepressants (TCAs), such as amitriptyline and nortriptyline. These are also very effective pain modulators, working through norepinephrine and serotonin reuptake inhibition, as well as other mechanisms like sodium channel blockade.

However, they come with a heavier side-effect burden, largely due to their anticholinergic effects. These include:

• Dry mouth
• Constipation
• Urinary retention
• Blurred vision
• Cognitive “fuzziness”

Important Clinical Considerations for TCAs:

• Drug Interactions: TCAs are heavily metabolized by the cytochrome P450 enzyme system in the liver, which is also responsible for metabolizing many other medications. This creates a high potential for drug-drug interactions, so a careful medication review is essential.
• Cardiac Risk: At high doses (typically over 100 mg), TCAs can cause QT prolongation on an EKG, which increases the risk of dangerous cardiac arrhythmias.
• Dosing for Pain vs. Depression: This is a critical distinction. For depression, a typical dose of a TCA might be 100 mg, 200 mg, or even higher. For pain, our doses are dramatically lower. We often start at just 10 mg at bedtime and titrate up slowly. This low-dose strategy maximizes the analgesic benefit while minimizing the risk of side effects, including cardiac risk.
• Patience is Key: Like SNRIs, TCAs do not work overnight. A therapeutic trial is considered to be six to eight weeks at an adequate dose. I always counsel my patients: “You didn’t get into this state of chronic pain in a day, and we’re not going to get you out of it in a day. We need to be patient and let the medication work.”

A Clinical Mission: Burning Mouth Syndrome

There is one condition where TCAs have proven to be so uniquely effective that I feel it is my personal public service announcement to share it: Burning Mouth Syndrome (BMS).

If you have never encountered it, BMS is a debilitating chronic pain condition that is exactly what it sounds like: a constant, severe burning sensation in the mouth, on the tongue, and on the lips, but with a completely normal oral exam. There is no visible cause. It typically affects post-menopausal women and can be triggered by a period of intense stress. Patients can suffer for years, seeing multiple specialists without a diagnosis or effective treatment.

In my clinical experience, and supported by a growing body of evidence, low-dose TCAs are often the most effective treatment. While newer interventions like sphenopalatine ganglion blocks are showing promise, the simplicity and efficacy of a TCA are hard to beat.

• My Protocol: I typically start with nortriptyline 10 mg at bedtime. I have the patient increase the dose by 10 mg each week until they reach 50 mg or experience significant relief, whichever comes first. It is very rare for a patient to need to go up to the full 50 mg.
• The Result: Within a few weeks, patients who have been miserable for years often report feeling better for the first time.

I hope that by planting the term “burning mouth syndrome” in your mind, the next time you encounter a patient with these perplexing symptoms, a lightbulb will go on, and you will remember that this is a real, treatable neuropathic pain condition.

Benzodiazepines and Pain: A Dangerous Misconception

I want to be unequivocally clear on this next point: Benzodiazepines are not pain medications.

This statement may seem obvious, but the use of benzodiazepines like diazepam (Valium) for musculoskeletal conditions like acute low back pain is still common. This practice is not supported by evidence and is potentially harmful.

Why We Must Avoid Benzodiazepines for Pain

1. Lack of Efficacy: There is no robust evidence that benzodiazepines provide meaningful relief for low back pain. In fact, studies have shown a failure to improve pain at 10-14 days compared to placebo. They are primarily muscle relaxants and anxiolytics, not analgesics.
2. Antagonism of Opioid Analgesia: This is a fascinating and critically important finding from a pharmacology perspective. Research has shown that benzodiazepines can act as antagonists to opioid analgesia. This means that when a patient takes a benzodiazepine and an opioid at the same time, the benzodiazepine can actually prevent the opioid from working effectively to relieve pain. This can lead to a dangerous cycle where the patient feels their pain is not controlled, leading them to request higher doses of opioids. At the same time, the benzodiazepine simultaneously increases the risk of respiratory depression. The combination is a recipe for disaster and is a major driver of accidental overdose deaths.
3. Risks of Long-Term Use: We know that long-term use of benzodiazepines is associated with cognitive impairment, increased risk of falls (especially in the elderly), dependency, and a difficult and dangerous withdrawal syndrome.

For muscle spasms associated with back pain, there are far better and safer options. Using a benzodiazepine for this indication introduces unnecessary risk with no proven benefit.

Navigating Opioids and Muscle Relaxants Safely

The modern pain care landscape requires a deep understanding of not just what to prescribe, but how to do so safely. This involves comprehending the intricate interactions between different drug classes, recognizing the limited role of some traditional therapies, and embracing novel, safer alternatives.

Understanding the Opioid–Benzodiazepine Interaction and Overdose Risk

As a clinician who manages musculoskeletal pain and coordinates care with an internal medicine physician, I pay close attention to how benzodiazepines and opioids interact. Large pharmacoepidemiologic and mechanistic studies have shown that concomitant use of benzodiazepines can blunt opioid analgesia and markedly increase overdose risk. Key evidence-based points:

• Benzodiazepines may directly impair opioid analgesic efficacy, contributing to diminished pain control and increased dose-seeking when co-prescribed.
• Overdose risk increases approximately tenfold in patients on high-dose opioids exceeding 200 morphine milligram equivalents (MME) daily, particularly when combined with benzodiazepines.
• The co-use of benzodiazepines and opioids has driven a substantial rise in admissions to substance use treatment programs, with reported increases exceeding 500% over a decade in some datasets.

Physiologic underpinnings:

• Both opioids and benzodiazepines depress respiratory drive via distinct receptor systems: opioids through mu receptor activation and downstream brainstem respiratory centers; benzodiazepines via GABA-A modulation that deepens sedation, reduces defensive arousal, and impairs ventilatory response to hypercapnia.
• Co-administration synergistically increases sedation and respiratory depression, especially in sleep-disordered breathing, COPD, obesity hypoventilation, and in older people.

Clinical reasoning:

• We use benzodiazepines sparingly and avoid routine co-prescription with opioids whenever possible. If anxiety requires treatment, we support non-benzodiazepine strategies such as CBT, sleep hygiene, SSRIs/SNRIs, buspirone, or targeted psychotherapy, under medical supervision. When benzodiazepines are indicated for short, clearly defined durations (e.g., an MRI for claustrophobia), we apply strict limits and educate patients about risks and driving precautions.
• Integrative chiropractic care contributes by reducing pain drivers and anxiety through manual therapy, breathing protocols, and graded movement, often making anxiolytics less necessary.

Cautious Anxiety Care and Multimodal Strategies

Appropriate anxiety treatment should not be neglected because of pain care concerns; rather, it should be managed safely with strategies that do not compound opioid risk, and with close oversight by internal medicine and behavioral health providers. In our clinic:

• We screen for anxiety, depression, sleep disorders, and catastrophizing (GAD-7, PHQ-9, PSQI, PCS).
• We prioritize non-pharmacologic strategies including:

• Cognitive behavioral therapy, mindfulness-based stress reduction (MBSR), and acceptance and commitment therapy (ACT).
• Breathing retraining, paced respiration, and heart rate variability (HRV) biofeedback to improve vagal tone.
• Structured exercise, which yields anxiolytic effects via endocannabinoid and serotonergic pathways.

• When medication is necessary, Dr. Cardenas oversees choices that minimize sedation and respiratory suppression.

The reason for this approach is that anxiety amplifies pain perception through limbic facilitation of nociception and reduced descending inhibition. Addressing anxiety improves pain outcomes and reduces opioid requirements.

Muscle Relaxants—Limited Efficacy and Clinical Nuance

When patients present with acute low back pain or sciatica, muscle relaxants are often considered. Evidence suggests:

• As a drug class, muscle relaxants offer limited benefit for sciatica. They may only provide modest short-term relief for acute low back pain localized to the back, not radicular leg pain. Many agents primarily depress the CNS rather than directly reduce pathologic spasm.

Diazepam:

• Not superior to tizanidine or cyclobenzaprine for musculoskeletal pain.
• Being a benzodiazepine, it carries sedation and dependency risks. In our clinic, diazepam is reserved for specific short procedural needs (e.g., MRI anxiety) under medical oversight.

Cyclobenzaprine:

• Chemically similar to tricyclic antidepressants (TCAs) and can interact with mood disorders.
• Reaches steady-state CNS depression in 3–4 days when dosed three times daily.
• We avoid it in bipolar disorder and in complex psychiatric cases unless coordinated with psychiatry, because TCA-like effects may destabilize mood.

Tizanidine:

• A central alpha-2 adrenergic agonist (like clonidine) indicated for spasticity.
• Short duration of action can be advantageous; patients can plan dosing around activities and avoid prolonged driving impairment.
• We monitor for hypotension, sedation, and hepatic effects.

Carisoprodol (Soma):

• Reclassified as a controlled substance due to abuse potential.
• Rarely used; when necessary, strictly short-term and under tight controls.

Baclofen:

• A GABA-B agonist indicated for spasticity; distinct from general CNS depressants.
• Abrupt discontinuation after long-term use can be dangerous; in intrathecal pump failure, immediate oral baclofen may be required to prevent severe withdrawal.
• Can alter seizure threshold, affect glycemic control, and exacerbate psychiatric symptoms.
• Has niche evidence in trigeminal neuralgia.

Clinical reasoning:

• We prefer non-pharmacologic strategies (manual therapy, graded movement, myofascial release, exercise) for muscle hypertonicity and spasm, reserving pharmacologic relaxants for short durations when function is severely limited.

Emerging and Advanced Pharmacologic Strategies

The field of pain management is constantly evolving. Here, I discuss some of the most promising and innovative therapies that are changing how we approach chronic pain, moving beyond traditional agents.

Low-Dose Naltrexone (LDN)—Glial Modulation and Pain

Low-dose naltrexone (LDN) is an emerging therapy in chronic pain. While naltrexone at 50 mg is used in addiction medicine, low doses (typically 1.5–4.5 mg) may exert paradoxical effects that modulate neuroimmune activity.

Mechanism:

• LDN transiently blocks opioid receptors, leading to compensatory upregulation of endogenous opioids and receptors after the blockade wears off.
• More importantly, LDN may inhibit Toll-like receptor 4 (TLR4) on microglia, the immune cells of the central nervous system. This action attenuates neuroinflammation and central sensitization, which are key drivers of chronic pain states.

Evidence and applications:

• Fibromyalgia: Small trials indicate significant reductions in pain and fatigue.
• Long COVID: Early studies and case series suggest symptom improvements, potentially via modulation of these neuroimmune pathways.
• Ehlers-Danlos syndrome: Anecdotal and case-based support exists for pain modulation, though robust data are still limited.
• Crohn’s disease: Trials in pediatric and adult populations show mucosal healing and symptomatic improvement with LDN.
• Dosing: We start at 1.5 mg nightly for 1–2 weeks, titrate to 3 mg, then 4.5 mg as tolerated. A compounding pharmacy must prepare this medication.

Safety:

• LDN is generally well-tolerated; vivid dreams and sleep changes may occur initially but often resolve. It does not block acute opioid analgesia when sufficiently high opioid doses are administered in emergencies.

Suzetrigine—A New Non-Opioid Analgesic Targeting Nav1.8

In February 2025, the FDA approved suzetrigine as a non-opioid analgesic for acute pain. It’s a two-week course agent that targets the voltage-gated sodium channel Nav1.8, which is prevalent in nociceptive (pain-sensing) neurons.

Mechanism:

• The Nav1.8 sodium channel plays a key role in propagating action potentials along pain fibers, particularly under inflammatory conditions. By selectively blocking Nav1.8, suzetrigine dampens nociceptive signaling without engaging opioid pathways, thereby avoiding opioid-related risks like respiratory depression and addiction.

Dosing:

• 100 mg loading dose, then 50 mg twice daily for up to two weeks.

Efficacy:

• Trials for acute pain showed it to be comparable to hydrocodone 5 mg twice daily, but not superior.

Clinical considerations:

• A potential hurdle is that insurance approvals may require failure of a scheduled opioid like hydrocodone first—a counterintuitive barrier considering suzetrigine is a non-scheduled, safer alternative.
• It may interact with certain oral contraceptives; we counsel young female patients to use alternative contraception for at least one month while taking this medication.

Integration with chiropractic care:

• For acute musculoskeletal injuries, suzetrigine can be paired with spinal care, soft tissue work, and early rehabilitation to reduce opioid exposure while restoring function.

Deep Dive into Opioid Pharmacology and Safe Management

When opioids are necessary, a profound understanding of their pharmacology, risks, and management strategies is non-negotiable.

Opioid Mechanisms, Receptor Pharmacology, and Clinical Decision-Making

Understanding opioid receptor pharmacology helps us prescribe safely.

Mechanism:

• Opioids act on mu, delta, and kappa receptors in the spinal cord and brain, modulating ascending and descending pain pathways. Mu receptors predominate for analgesia but also slow GI motility, causing constipation.
• Mixed agonist-antagonists like buprenorphine are partial mu agonists and kappa antagonists. This unique profile creates a “ceiling effect” on respiratory depression, making them a safer option than full agonists.

Clinical insights:

• Opioids can reduce diuretic efficacy via antidiuretic hormone modulation; in cardiac or primary care contexts, we consider opioid effects if a patient’s diuretic response is blunted.

Buprenorphine for Pain—Less Respiratory Depression, Elderly-Friendly Options

Buprenorphine formulations for pain include the Butrans patch and Belbuca buccal film.

Why buprenorphine:

• As a partial mu agonist with kappa antagonism, it carries a lower risk of respiratory depression compared to full agonists like morphine or oxycodone.
• The Butrans patch provides steady analgesia with a weekly application, starting as low as 5 mcg/hour. This makes it particularly useful for elderly patients, those with compression fractures, or cases where consistent low-dose analgesia is needed to support activity without heavy sedation.

Perioperative note:

• Current recommendations from leading anesthesiology societies do not require stopping buprenorphine before surgery; we continue the medication and coordinate with the anesthesia team for intraoperative and postoperative pain management strategies.

Methadone—A Powerful Tool with Complex Kinetics

Methadone can be highly effective due to its dual action on mu receptors and NMDA antagonism, addressing both nociceptive and neuropathic pain components. However, its complexity demands expert management.

Cautions:

• Its half-life varies widely (8–59 hours). Dose increases can accumulate, producing delayed toxicity and overdose days later.
• It carries a risk of QT prolongation on an EKG, which can lead to dangerous cardiac arrhythmias. This risk increases at higher doses (>80–100 mg/day), though pain management doses are often lower.
• Its analgesic duration is shorter (4–6 hours) than its long half-life, which is why split dosing is often used in pain care.

Clinical policy:

• If you don’t know methadone well, you should avoid initiating it. In our clinic, we consider methadone only in select, complex cases with cardiology oversight and titrate it extremely slowly.

Opioid-Induced Constipation and Peripherally Acting Mu Receptor Antagonists

Opioid-induced constipation (OIC) is a near-universal side effect that must be managed proactively and explicitly.

Clinical pearls:

• Avoid bulking agents like psyllium (Metamucil) when a patient is on opioids. Opioids reduce gut motility, and adding bulk to a system that isn’t moving can effectively create “concrete,” worsening the problem.
• Ask specific questions: “How often are you having a bowel movement?” “What is the consistency?”, “Do you feel like you’ve completely evacuated?” If there is concern, we obtain an abdominal flat plate x-ray to assess for obstruction.

Peripherally acting mu-opioid receptor antagonists (PAMORAs):

• Agents such as methylnaltrexone (Relistor) and naloxegol (Movantik) are designed to block mu receptors in the gut without crossing the blood-brain barrier. This reverses constipation without affecting central analgesia.
• Relistor is available as a subcutaneous injection, which is highly useful in patients, such as those with head and neck cancer, who may have difficulty swallowing pills.
• Patients can expect a spontaneous bowel movement within hours of administration.

Practical Frameworks for Safe and Effective Pain Management

Our philosophy is built on structured, evidence-based frameworks that prioritize safety, function, and shared decision-making.

Risk Assessment and Monitoring

Before initiating any controlled substance, especially opioids, we perform a thorough risk assessment:

• Physical exam and functional assessment: This includes range of motion, a neurologic screen, and checking for red flags.
• Risk screening tools: We use validated tools like the SOAPP (Screener and Opioid Assessment for Patients with Pain) or COMM (Current Opioid Misuse Measure) to assess risk for aberrant behaviors.
• Prescription Monitoring Program (PMP): We check the state database to review a patient’s prescription history for controlled substances.
• Documentation: We meticulously document trials and failures of other therapies or contraindications (e.g., NSAIDs contraindicated due to anticoagulation).
• Medication Agreement: We establish a formal medication agreement that defines goals (focused on function, sleep, and work capacity, not just pain scores), responsibilities, and refill policies.

Equianalgesic Dosing Caveats

Standard opioid conversion charts can be dangerously misleading. They do not account for individual differences in metabolism (e.g., via the CYP450 enzyme system) or drug interactions that can alter a drug’s effective potency. Morphine, for example, does not rely on the same CYP2D6/3A4 pathways as oxycodone, meaning patients can respond very differently based on their unique genetics and other medications. All conversions must be done cautiously, typically with a 25-50% dose reduction to account for incomplete cross-tolerance.

Safe Storage, Disposal, and Narcan for Risk Mitigation

Opioid safety extends beyond the clinic and into the household.

• Safe storage and disposal: Most patients have leftover opioids after a procedure and keep them. We proactively counsel them on safe storage and provide resources for disposal, with take-back programs being the preferred method. The FDA also endorses flushing certain high-risk medications to prevent accidental ingestion by children or pets if a take-back program is not available.
• Narcan (naloxone): Naloxone is for a risky drug, not a risky patient. We believe in co-prescribing or recommending household naloxone for patients on chronic opioid therapy. It is a safety measure that heightens vigilance for everyone. We teach caregivers that naloxone can be administered to any unresponsive person without harm and that redosing may be necessary. We advise patients to store naloxone in an easily accessible location, separate from other medications.

Practical Dosing Strategies and Temporal Pain Patterns

Often, effective pain management is about timing. Many patients mis-time their medication relative to their worst pain. If a patient’s pain consistently spikes at 4 pm and their dose is at noon, we may advise shifting the dose to 3 pm (if medically appropriate) to cover the pain period better. We educate patients on:

• Chronopharmacology: Understanding how a drug’s onset and duration intersect with daily rhythms and mechanical loads.
• Activity pacing: Using short-acting analgesics pre-emptively before a physical therapy session can enable better participation without causing over-sedation.

Real-World Patients and Function-Focused Outcomes

Our goal is always to improve function and quality of life. Patients like Mike and Sheila illustrate these principles:

Mike:

• A 56-year-old construction worker with lumbar disc bulges and facet arthropathy. He is post-myocardial infarction and on anticoagulants, which contraindicates NSAIDs. He receives epidural injections and uses hydrocodone once or twice daily to keep him working and engaged with his triplets. He avoids muscle relaxants as he does not have significant muscle spasm. Our plan for him emphasizes spinal biomechanics, targeted manual therapy, core stabilization, and job-specific conditioning to minimize opioid reliance while protecting his cardiac and musculoskeletal health.

Sheila:

• An 84-year-old with a prior L4–S1 fusion and severe adjacent segment degeneration. Poor bone density and respiratory issues preclude further surgery. An older-generation spinal cord stimulator relieved her radicular pain but not her axial low back pain. She uses extended-release oxycodone twice daily plus a short-acting opioid for breakthrough pain, which allows her to maintain daily function and spend time with her husband. For Sheila, our care, always under Dr. Cardenas’ medical supervision, incorporates gentle chiropractic techniques, balance training for fall prevention, osteoporosis-sensitive loading exercises, and a strict bowel regimen to mitigate opioid side effects.

These are regular people who have often tried and failed many other options. Our duty is to help them maintain dignity, function, and safety with the least harm possible.

The Foundational Role of Integrative Chiropractic and Functional Medicine

Pharmacology is a tool, but it is not the solution. True recovery comes from restoring the body’s innate function. This is where our integrative model, combining chiropractic, functional medicine, and rehabilitation, becomes paramount.

Integrating Chiropractic Care: Restoring Function and Reducing Reliance on Medication

Everything we have discussed so far focuses on managing pain symptoms through pharmacology. This is often a necessary and important part of the treatment plan. However, it is only one piece of the puzzle. At Injury Medical Clinic, our philosophy is to use these tools to”“urn down the volume” on the pain enough so that the patient can engage in the most important part of their recovery: restoring function.

My role as a Doctor of Chiropractic, working in concert with Dr. Cardenas’s medical oversight, is to address the underlying biomechanical and structural issues that are often the root cause or a major perpetuating factor of the pain.

• Spinal Manipulation and Mobilization: For conditions like chronic low back pain or radicular pain, gentle and precise chiropractic adjustments can help restore proper motion to spinal joints, reduce nerve irritation, and decrease local inflammation. This directly addresses the “peripheral generator” of pain signals. Physiologically, these adjustments produce segmental inhibition via mechanoreceptor activation, modulating dorsal horn excitability and reducing nociceptive transmission. They can also enhance descending inhibitory pathways.
• Soft Tissue Therapies: Techniques like myofascial release, trigger point therapy, and instrument-assisted soft tissue mobilization are used to break down adhesions and scar tissue in muscles and fascia. This improves flexibility, increases blood flow, and reduces the muscular tension that accompanies chronic pain.
• Therapeutic Exercise and Rehabilitation: This is the cornerstone of long-term success. Once pain is reduced, we introduce a targeted rehabilitation program, including McKenzie method/directional preference exercises, neuromotor re-education to improve movement patterns, and core stabilization to enhance load distribution and reduce mechanical stress. This is not just “giving someone a sheet of exercises” but a carefully progressed program to restore functional capacity.
• Patient Education: We spend significant time educating patients about posture, ergonomics, and body mechanics to prevent re-injury and empower them to take an active role in their health.

By integrating these hands-on, function-focused therapies, we can often reduce or even eliminate the need for long-term medication. The goal is to use medications as a bridge—a temporary tool to make the patient comfortable enough to participate in the active rehabilitation that will lead to a true, lasting recovery. This synergy between evidence-based medicine and advanced chiropractic care is the future of effective and responsible pain management.

Functional Medicine Integration—Metabolic, Inflammatory, and Neuroimmune Factors

Functional medicine complements our approach by targeting systemic drivers of pain:

• Diet and inflammation: We guide patients on anti-inflammatory dietary patterns to reduce inflammatory signaling molecules (like IL-6 and TNF-α) that sensitize pain pathways.
• Microbiome Health: Gut dysbiosis can influence neuroimmune crosstalk. Addressing gut health supports overall comfort and can improve medication tolerance.
• Sleep Optimization: Sleep is critical for restoring the brain’s natural pain inhibitory circuits. We prioritize sleep hygiene and coordinate with sleep medicine specialists when indicated.
• Micronutrients: Deficiencies in nutrients like Vitamin D, magnesium, and omega-3s can influence muscle function and pain perception. Dr. Cardenas’ oversight ensures the safe integration of supplements with prescription medications.

Personal Injury Care—Documentation, Risk, and Recovery

Personal injury cases require an additional layer of expertise. Our team approach ensures:

• Accurate Documentation: We meticulously record the mechanism of injury, timeline, pain progression, interventions tried and failed, and functional impairments.
• Comprehensive Risk Assessment: We identify red flags (e.g., fracture, cauda equina syndrome), comorbidities, and psychosocial risks like PTSD that can complicate recovery.
• Coordinated Recovery Plans: We combine chiropractic care, physical therapy, and cognitive support to help patients return to work and daily life, coordinating with attorneys and insurers while keeping patient safety and clinical evidence at the forefront.

Closing Thoughts: A Compassionate, Evidence-Based Path Forward

There aren’t endless pharmacologic options; that’s why integrative care matters. The real key is often a combination of precise timing, strategic dosing, and robust multimodal support. Medications are one component. The broader framework—manual care, rehabilitation, functional medicine, and careful medical oversight—creates durable outcomes.

In our clinic, Dr. Cardenas and I work side by side to ensure that each patient’s plan honors safety, science, and the person’s individual goals. Pain management is a journey worth taking with a dedicated team. If you are seeking a team that integrates chiropractic care with internal medicine and functional strategies, we welcome conversations and collaborative care. As my clinical work and professional background reflect, our commitment is to this patient-centered, integrative model.

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References

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