Neck Pain in Adults _________________________________________________________________________
Topical Analgesics Transdermal analgesic formulations are used for systemic drug delivery, absorption, and distribution. In contrast, topical analgesics are used for drug delivery to local tissue while avoiding systemic exposure. Topical analgesics have evolved to gain acceptance as analgesic options and have the potential to reduce pain in some conditions while avoiding the side effects of systemic analgesics. Topical analgesics include FDA-approved and compounded formulations. FDA-Approved Topical Analgesics FDA-approved topical analgesics include NSAID gel or cream, 5% lidocaine patch or plaster, and 8% capsaicin patch [208]. Topical NSAIDs are increasingly favored in musculoskeletal conditions to avoid the systemic adverse effects of oral NSAIDs, with diclofenac and ketoprofen the most-studied topical NSAIDs. In acute pain, benefit in sprains or strains has good evidence, but the formulation used is critically important; this same consideration may also apply to chronic conditions. Use in chronic musculoskeletal conditions assessed over 6 to 12 weeks showed good pain relief beyond inert carrier in a minority of patients with knee osteoarthritis, limited benefit in hand osteoarthritis, and no evidence in other chronic painful conditions [209; 210]. Emerging data suggest the capsaicin 8% patch and lidocaine 5% patch or medicated plaster may both be effective in the treatment of chronic low back pain (and by extension, chronic neck pain) with a neuropathic component [71]. Sodium channels expressed on nerve fibers become altered in neuropathic pain to enhance excitatory neurotransmission [69]. Lidocaine prevents the generation of pathologic nerve excitation by blocking sodium channels. Topical lidocaine may be beneficial when neuropathic pain is localized, because the maximum penetration depth is 8–10 mm. Lidocaine patches are applied to the painful area for 12 hours, followed by a patch-free interval of 12 hours [68]. An uncontrolled study evaluated 5% lidocaine plaster in 23 patients with cervical or lumbar disk herniation and peripheral neuropathic pain (radiculopathy). Compared with baseline, mean pain intensity scores following average treatment duration of eight months decreased from 8.3 to 3.1. Treatment was well-tolerated [211]. In neuropathic pain, transient receptor potential (TRP) channels induce and maintain spontaneous pain and thermal hyperalgesia. The TRPV1 agonist capsaicin activates TRP channels, and desensitization that follows can reduce neuropathic pain [70; 71]. Capsaicin 8% patch was effective in painful radiculopathy when placed on involved spinal nerve dermatomes. Fifty patients with cervical or lumbar radiculopathy were evaluated 12 weeks after a single treatment. Among patients with pain duration 3 months, 24 months, or >24 months, 50%, 71%, and 39% achieved ≥30% pain
reduction, respectively. Four patients experienced application site pain or pruritus [212]. Compounded Analgesic Formulations Analgesic medications compounded for topical use are gaining popularity in chronic pain management. Compounded analgesic formulations have the potential advantages of FDA-approved topical analgesics, but with a broader range of options, including ketamine, clonidine, gabapentin, baclofen, and phenytoin [208]. Compounded analgesic formulations typically combine three or more analgesic drugs to achieve multiple complementary effects at lower doses of each drug [213]. Some evidence suggests greater pain reduction with compounded versus FDA-approved topical analgesics. In an uncontrolled study, 2,177 patients with chronic pain received one of three treatments [214]: • Cream I: Flurbiprofen (20%), tramadol (5%), clonidine (0.2%), cyclobenzaprine (4%), and bupivacaine (3%) • Cream II: Flurbiprofen (20%), baclofen (2%), clonidine (0.2%), gabapentin (10%), and lidocaine (5%) • Voltaren gel: 1% diclofenac sodium (an FDA- approved NSAID formulation) Pre-treatment chronic extremity, joint, musculoskeletal, or neuropathic pain intensity (0–10 scale) in all groups was severe (range: 7.9–8.4). Post-treatment pain intensity scores decreased 37% with cream I, 35% with cream II, and 19% with Voltaren gel. The compounded analgesic formulations did not differ in efficacy, and both were superior to Voltaren [214]. Many small uncontrolled trials show compounded analgesic formulations’ efficacy, but this approach must balance local penetration against systemic exposure and potential toxicity. Compounding is not FDA-regulated; vehicle formulation and active drug concentration should be standardized for greater confidence in compounded analgesic formulations safety and efficacy [215]. Cannabinoids Cannabinoids, which include plant Cannabis , cannabidiol extracts, and pharmaceutically synthesized molecular constituents of Cannabis , are increasingly available to patients with pain through state-level enactment of medical access. Cannabinoids are seldom considered first-choice therapeutic options but are used instead in patients for whom standard therapies are ineffective or intolerable, either as sole therapy or more typically as an add-on to the current regimen [216]. Cannabis has been safely co-administered with a wide range of other drug agents and acts synergistically with opioids to enhance analgesia and allow opioid dose reduction. Chronic pain treatment often requires multiple drug agents that target different pain mechanisms, and the novel mechanism and
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