Opioids suppress spontaneous activity of polymodal nociceptors in rat paw skin induced by ultraviolet irradiation.
Changes in chemical sensitivity of peripheral nociceptors following injury or inflammation have been studied in in vitro preparation of the saphenous nerve-hind paw skin from adult rats. Heat hyperalgesia in the hind paw was induced by a prior ultraviolet irradiation and the skin from these animals was investigated five days later. Polymodal nociceptors were quiescent in normal skin but were spontaneously active in the majority of fibres after ultraviolet exposure. Capsaicin-induced activation of fine fibres was enhanced after ultraviolet pretreatment. Direct administration of morphine, DAGOL (mu-receptor agonist) and U-69593 (kappa-receptor agonist), but not DPDPE (delta-receptor agonist) to the receptive field produced a concentration-related and naloxone-reversible suppression of spontaneous firing in polymodal nociceptors of ultraviolet-treated skin. Morphine did not reduce the activity of fibres in normal skin when these were driven by KCl depolarization. These data show that polymodal nociceptors change their activity and sensitivity to exogenous chemicals following the induction of peripheral hyperalgesia by ultraviolet irradiation. Specifically, evidence is provided for the expression of opioid sensitivity and inhibition of polymodal nociceptor activity through mu- and kappa-opioid receptors. These observations may account for peripheral antinociceptive actions of opioids during specific states of peripheral hyperalgesia.
Andreev
N
N
Sandoz Institute for Medical Research, London, U.K.
Urban
L
L
Dray
A
A
D000595:Amino Acid Sequence; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D003864:Depression, Chemical; D004558:Electric Stimulation; D005528:Foot / Q000294:innervation; D006930:Hyperalgesia / Q000503:physiopathology; D008297:Male; D008969:Molecular Sequence Data; D009270:Naloxone / Q000494:pharmacology; D009294:Narcotics / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects* / Q000528:radiation effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects* / Q000294:innervation / Q000528:radiation effects; D014466:Ultraviolet Rays
D009294:Narcotics; D009270:Naloxone; D002211:Capsaicin