Mechanisms of Topical Analgesics in Relieving Pain in an Animal Model of Muscular Inflammation

• Published in: Pain medicine (Malden, Mass.) Vol. 14; no. 9; pp. 1381 - 1387
• Main Authors: Duan, Wan‐Ru, Lu, Jie, Xie, Yi‐Kuan
• Format: Journal Article
• Language: English
• Published: England Oxford University Press 01.09.2013
• Subjects: Action Potentials - drug effects; Administration, Cutaneous; Afferent Pathways - drug effects; Analgesics; Analgesics - administration & dosage; Animals; Capsaicin - administration & dosage; C‐Fiber Activation; Disease Models, Animal; Electrophysiology; Female; Male; Muscular Inflammatory Pain; Myositis - drug therapy; Nerve Fibers, Unmyelinated - drug effects; Pain; Plants, Medicinal; Rats; Rats, Sprague-Dawley; Rodents; Skin - drug effects; Skin - innervation; Skin Plasma Extravasation; Tibet; Topical Analgesics; Tibet; Topical Analgesics; Skin Plasma Extravasation; Muscular Inflammatory Pain; C-Fiber Activation
• ISSN: 1526-2375; 1526-4637
• DOI: 10.1111/pme.12199

Objective To investigate the possible mechanisms of topical analgesics in relieving pain in an animal model of muscular inflammation. Methods Adult Sprague‐Dawley rats of both sexes were injected with complete Freund's adjuvant to induce inflammation in the anterior tibialis muscle of left hindlimb. One of two types of topical analgesics: Xiaotong Tiegao (XTT), a Tibetan herb compound, or Capzasin (CAP), a cream containing 0.1% capsaicin, was applied to the skin over the inflamed anterior tibialis muscle. The following experiments were performed: pain behavioral tests, evaluation of plasma extravasation in the affected limb, and electrophysiological recordings of afferent nerve fibers. Results The behavioral experiments demonstrated that applications of either type of topical analgesic to the skin over the inflamed muscle significantly reduced muscular inflammatory pain, as indicated by the increased weight bearing capacity on the affected hindlimb (with latencies of 10 minutes for XTT and 1–2 hours for CAP). Meanwhile, both analgesics caused plasma extravasation in the affected skin. Electrophysiological recordings from the afferent fibers in the related cutaneous nerve indicated that topical analgesics selectively activated C‐fibers, but not A‐fibers innervating the same region of receptive field. The latency and duration of C‐fiber activation was similar to those of the reduction of muscular inflammatory pain. On the contrary, topical analgesics substantially decreased C‐fiber afferent spontaneous firing in the nerve innervating the inflamed muscle. Moreover, denervation of the affected skin blocked the analgesic effects of both topical analgesics in muscular inflammatory pain. Conclusion This study suggests that topical analgesics may reduce the nociceptive input from inflamed muscles via a reflex mechanism by activating the cutaneous nociceptive afferents.