Topical Pain Medications and Their Role in Pain Management

The goal of this chapter is to review topical pain medications and their place in therapy. The ability to bypass first-pass metabolism and minimize systemic side effects allows for safer options, especially for patients on multiple medications. There is a growing interest in utilizing compounded preparations to improve adherence and efficacy.

Topical pain medications have applications in many different disease states. They can be utilized to help manage pain symptoms or combined to offer synergistic effects. Neuropathic pain (NP) is a debilitating condition that impairs patient quality of life. The international association for the study of pain defines NP as “pain caused by a lesion or disease of the somatosensory nervous system.”1 Patients will often present with burning, tingling, and the description of needles poking their skin. Due to variability in subjective response to analgesia, oftentimes patients will try multiple different therapies to try and manage pain.

Capsaicin

  • • Capsaicin is a lipophilic compound that diffuses poorly into aqueous solutions in the body, making it ideal for topical, localized delivery. It functions by acting as a vanilloid receptor agonist, binding at the transient potential vanilloid receptor 1 (TRPV1). It acts by depleting substance P from sensory nerve endings to modulate neuropathic pain. Chronic exposure to capsaicin can produce a persistent local effect on cutaneous nociceptors, which is best described as “defunctionalization” and is constituted by reduced spontaneous activity and a loss of responsiveness to a wide range of sensory stimuli.2-3
  • • A literature review by Pickering et al.4 was performed to evaluate local treatments for localized neuropathic pain. Results showed that both topical 8% capsaicin and topical 5% lidocaine were efficacious for localized neuropathic pain. Both were well-tolerated and safe when used long term and should be considered for first-line use, especially in elderly patients, patients with multiple comorbidities, and polypharmacy.
  • • A Cochrane review was done to explore high-dose topical capsaicin for neuropathic pain in adults. Randomized controlled trials studying capsaicin 8% patches were included. Four studies featuring 1272 patients treated for postherpetic neuralgia showed significantly improved efficacy outcomes over controls. At both 8 and 12 weeks of therapy, more patients reported feeling much or very much better using high-concentration capsaicin than controls. Two studies involved 801 participants treated for HIV neuropathy. Both studies showed an average reduction in pain intensity by 30% with high-concentration capsaicin. Local adverse reactions were common, such as pruritus, erythema, and burning at the application site.5
  • • A systematic review was done to evaluate the evidence of both oral and topically applied medications in the treatment of osteoarthritis. Capsaicin gel was effective in the management of osteoarthritis. Five randomized controlled trials (RCTs) were evaluated and showed treatment efficacy. In three of the trials, patients applied 0.025% capsaicin four times daily for 4-12 weeks. In the fourth study, 0.015% capsaicin was applied once daily for 6 weeks. The fifth study utilized 0.075% capsaicin four times daily for 4 weeks. In all trials, capsaicin showed a significant improvement in pain compared to placebo. All trials also showed a significant improvement in pain upon movement. Adverse effects included redness and burning sensation.6
  • • A randomized, double-blind, crossover, placebo-controlled clinical study conducted by Kulkantrakorn et al.7 investigated the efficacy and safety of a 0.075% topical capsaicin lotion on painful diabetic neuropathy. The study included patients with both types 1 and 2 diabetes mellitus who had suffered from painful diabetic neuropathy for at least 1 month. Treatment intervention was studied for 8 weeks followed by a 4-week washout period before crossing over to the other treatment. Participants were instructed to apply the capsaicin lotion to the painful area three times a day. The primary outcome of this study was a reduction in mean pain score from baseline, which was assessed using the visual analog scale (VAS). The secondary endpoints included score changes in neuropathic pain scale, assessing pain with the short form McGill Pain Questionnaire, and the proportion of patients with pain score reductions of 30% to 50%. Safety was also investigated at each visit during the study. There were no significant improvements in pain control compared to placebo for any of the pain measures or for the proportion of patients with pain score reductions of 30% to 50%. There were some adverse effects seen from the group using capsaicin including burning, edema, and erythema. This study failed to show that there was a benefit from using a capsaicin lotion with a concentration of 0.075%.
  • • Casanueva et al.8 conducted a two-armed randomized clinical trial testing the effectiveness of Sensedol®, a 0.075% capsaicin topical treatment, in patients with severe fibromyalgia. The primary outcome of this study was a change in the overall score of pain. The secondary outcomes included other fibromyalgia-related variables. A total of 130 patients were treated for 6 weeks and evaluated both at the beginning and end of the 6-week treatment period and again at 6 weeks post-treatment. Participants were instructed to apply the cream three times a day to the affected area. The researchers found that at the end of the 6-week treatment period, patients had shown significant improvements in myalgic score. Six weeks after treatment, patients showed significant improvement in several clinical outcomes, including myalgic score and pressure pain threshold, but the VAS score for pain did not show statistically significant improvement. The overall conclusion from this study was that 0.075% capsaicin cream can provide short-term improvement. The researchers acknowledged that the treatment duration was short and recognize that further studies are needed.
 
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