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15 Articles in Volume 18, Issue #5
Chronic Pelvic Pain: The Need for Earlier Diagnosis and Diverse Treatment
Cross-Linked Hyaluronic Acid for the Management of Neuropathic Pelvic Pain
Fentanyl: Separating Fact from Fiction
Gender Bias and the Ongoing Need to Acknowledge Women’s Pain
Letters to the Editor: 90 MME/day Ceiling; Ehlers-Danlos; Redefining Pain
Post-Menopausal MSK Pain and Quality of Life
PPM Welcomes Dr. Fudin and Dr. Gudin as New Co-Editors
Practitioner as Patient: Understanding Disparities in CRPS
States Take Action to Manage Opioid Addiction
Step-by-Step Injection Technique to Target Endometriosis-Related Neuropathic Pelvic Pain
The Many Gender Gaps in Pain Medicine
The Need for Better Responses to Vulvar Pain
Topical Analgesics for Common, Chronic Pain Conditions
Topical Medications for Common Orofacial Pain Conditions
What’s the safest, effective way to taper a patient off of opioid therapy?

Topical Analgesics for Common, Chronic Pain Conditions

A look at alternative and combination therapies for treating musculoskeletal pain, osteoarthritis, post-herpetic neuralgia, and peripheral neuropathy.
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Topical drug delivery offers a potential advantage of achieving therapeutic concentrations locally with minimal systemic absorption, thereby reducing systemic adverse effects. Topical analgesics may be useful in treating acute and chronic pain caused by a wide range of conditions, from musculoskeletal (MSK) pain to neuropathic pain syndromes. These agents are available in a variety of formulations including creams, ointments, gels, lotions, and patches. Application site, vascularity of tissue, surface area, and duration of application are important factors affecting the absorption and distribution of the active ingredient into tissues. For a local medication to be absorbed, it must penetrate the stratum corneum by either an intracellular, paracellular, or transappendageal route. Mucosal surfaces are often easier to penetrate than keratinized surfaces due to absence of the stratum corneum. The addition of skin permeation enhancers (eg, solvents, surfactants, urea) and physical measures (eg, skin exfoliation, patch delivery, iontophoresis) may further improve drug delivery.1,2

Topical drug delivery differs from transdermal drug delivery in that topical formulations are intended to have effects at the site of application whereas transdermal formulations are absorbed into the bloodstream and produce systemic effects.1 A patch may be considered topical if it produces local effects or transdermal if it produces systemic effects. For example, a fentanyl patch is considered a transdermal formulation. This article reviews the efficacy of select topical analgesics that are commonly used in clinical practice. Table I provides a brief overview of these agents.

Counterirritants and Rubefacients

Counterirritants represent an interesting class of topical analgesics that act to increase nerve stimulation, rather than decrease it.2 There has been some confusion among the pain management community regarding which agents are classified as counterirritants; however, salicylates, camphor, menthol, and capsaicin are usually classified within this category. Counterirritants come in a variety of over-the-counter formulations, including creams, lotions, gels, ointments, sprays, and patches.

The theory behind counterirritants’ mechanism of action is that irritation of sensory nerve endings helps alter or offset the original pain in the muscle or joints innervated by the same nerves.3 Some counterirritants, such as salicylates, are structurally related to aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) but they do not penetrate underlying tissues. These counterirritants are further classified as rubefacients and their primary action is to irritate the skin producing local vasodilation.

There is limited evidence supporting the role of counterirritants for management of acute injuries or chronic pain. A systematic review evaluated data from three double-blind, placebo-controlled trials of 182 patients with acute pain and from six trials of 429 patients with chronic pain.3 All studies included salicylate application. Among those with acute pain, the number of patients needed to treat (NNT) was 2.1 to achieve at least 50% pain relief compared to placebo at 7 days. For chronic pain, the NNT for topical salicylate was 5.3 (95% CI 3.6 to 10.2) to achieve at least 50% pain relief compared with placebo at 14 days. On the other hand, the NNT for topical NSAIDs was 3.1 (95% CI 2.7 to 3.8) with the same comparator group (placebo) in similar conditions with similar durations.

A Cochrane review evaluated seven randomized controlled studies involving just under 700 participants with acute pain, and nine studies involving just under 600 participants with chronic pain.4 The NNT for acute pain was 3.2 (95% CI: 2.4 to 4.9) compared to placebo. However, when lower quality studies were excluded from the analysis, there were no significant differences between topical counterirritants and placebo. Among those with chronic conditions, the NNT was 6.2 (95% CI: 4 to 13) compared to placebo.

Current clinical usage of counterirritants and rubefacients is for the short-term treatment of mild to moderate MSK pain due to injury. Evidence of counterirritants effectively treating chronic pain conditions is limited; efficacy is not robust enough to support their widespread use.


Capsaicin, an active component of chili peppers, is a transient receptor potential vanilloid-1 receptor (TRPV1) agonist.2 Activation of TRPV1 channels on nociceptive nerve fibers often results in reduced initiation and transmission of pain signals to the spinal cord. Capsaicin induces a mass release of Substance P leading to its depletion. This process often leads to an initial excitation of sensory neurons followed by desensitization after repeated use.

Capsaicin is available over-the-counter in topical cream, liquid, gel, and lotion dosage forms for the treatment of MSK and joint pain associated with arthritis. An 8% patch formulation, Qutenza, is available by prescription as a patch and is FDA-approved for the treatment of neuropathic pain associated with post-herpetic neuralgia (PHN). Qutenza treatments may only be performed by healthcare providers and need to be repeated once every 3 months or longer.5 Initial response to the topical patch may be seen in individuals at approximately one week compared to over-the-counter formulations, which may take upwards of 6 weeks before relief is observed.5,6

Overall, capsaicin offers an affordable therapy for MSK, joint, and neuropathic pain. Its downside is the duration and frequency of use required to achieve relief. Often, an initial use of capsaicin enhances analgesia, rather than pain relief. Since consistent use is needed, patient compliance should be a determining factor when recommending capsaicin as a treatment.

Topical NSAIDs: Diclofenac

Diclofenac is an NSAID that exhibits antipyretic, analgesic, and anti-inflammatory properties.7,8 The primary mechanism of diclofenac is reversible inhibition of cyclooxygenase (COX)-1 and 2 enzymes, resulting in decreased formation of prostaglandin precursors. Prostanoids are involved in the modulation of transduction and transmission of nociceptive pain signals. COX-2 is found expressed in injured tissue and is a main source of prostanoid production in inflammation.

Topical NSAIDs enhance penetration at the source of inflammation, allowing the medication to concentrate specifically on peripheral COX enzymes while avoiding side effects often observed with systemic use.8 Diclofenac is the only NSAID commercially available in topical formulations in the United States; see Table II for specific formulations and recommended dosing regimens.9-11 Topical diclofenac is available outside the US without a prescription. Of note, diclofenac 3% gel (Solaraze) is approved for actinic keratosis and does not carry an indication for pain.12

Last updated on: August 2, 2018
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Topical Medications for Common Orofacial Pain Conditions