Morphine Directly Inhibits Nociceptors in Inflamed Skin
Wenk HN, Brederson JD, Honda CN.
Department of Neuroscience, University of Minnesota,
Minneapolis, MN, USA;
Graduate Program in Neuroscience,
University of Minnesota, Minneapolis, MN, USA.
J Neurophysiol. 2005 Dec 7;
ABSTRACTPeripherally delivered opiates attenuate mechanical and thermal hyperalgesia in experimental models of inflammation, suggesting that activation of peripheral opioid receptors decreases the excitability of nociceptors in inflamed tissues. The current study examines the effects of peripheral morphine sulphate on response properties of sensory neurons in healthy and inflamed skin. 185 afferent units were isolated from tibial nerve of rats using an in vitro glabrous skin-nerve teased-fiber preparation. Of these, 107 units were from normal healthy skin, and 78 were from inflamed skin 18 hours after intraplantar injection of complete Freund's adjuvant. As a population, C-fiber units innervating inflamed skin exhibited properties characteristic of sensitization when compared with units innervating healthy control skin. Mechanical thresholds were lowered, responses to noxious mechanical and thermal stimuli were elevated, a greater proportion of units were spontaneously active, and the average rate of spontaneous discharge was higher. Response properties in other conduction velocity groups remained unchanged. Fifty-eight percent of C and C/Adelta nociceptors innervating inflamed skin were opiate-sensitive, and their excitability was attenuated by direct application of morphine to their receptive fields. All morphine-sensitive units were nociceptors from inflamed skin with conduction velocities less than 1.3 meters per second. Morphine effects were concentration-dependent and naloxone-sensitive, indicating that the effects were receptor-mediated. These findings provide direct evidence that morphine acts through peripheral opioid receptors to inhibit the activity of cutaneous nociceptors under conditions of inflammation.Morphine: structure
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