Peripheral effects of morphine in neuropathic rats: role of sympathetic postganglionic nerve fibers.
We studied the contribution of peripheral opioid receptors to the morphine-induced antinociception in rats with a spinal nerve ligation-induced neuropathy. Intraplantar (i.pl.) injection of morphine produced a stronger suppression of nociceptive reflex responses of the neuropathic limb following ipsilateral, than contralateral, administration, whereas the morphine-induced effect on the control limb was independent of the injection side. Antinociception induced by systemically administered morphine was significantly attenuated by i.pl. injection of a peripherally acting opioid receptor antagonist in neuropathic but not in sham-operated rats. Following chemical sympathectomy with 6-hydroxydopamine, antinociception was achieved at a lower dose ipsilaterally, than contralaterally, following i.pl. administration of morphine, and the morphine-induced antinociception was attenuated by a peripherally acting opioid receptor antagonist. These results indicate that peripheral opioid receptors may contribute to the morphine-induced antinociception in the spinal nerve ligation-induced model of neuropathy. Sympathectomy of the neuropathic limb may underlie, at least partly, the increased peripheral efficacy of morphine in neuropathy.
Pertovaara
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Department of Physiology, Institute of Biomedicine, University of Turku, Kiinamyllynkatu 10, FIN-20520 Turku, Finland. Antii.Pertovaara@utu.fi
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D000701:Analgesics, Opioid / Q000008:administration & dosage*; D000818:Animals; D006614:Hindlimb; D007279:Injections, Subcutaneous; D008026:Ligation; D008297:Male; D020422:Mononeuropathies / Q000139:chemically induced / Q000188:drug therapy*; D009020:Morphine / Q000008:administration & dosage*; D016627:Oxidopamine; D010147:Pain Measurement / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology; D013127:Spinal Nerves / Q000187:drug effects / Q000502:physiology; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects* / Q000502:physiology*; D013565:Sympatholytics
D000701:Analgesics, Opioid; D011957:Receptors, Opioid; D013565:Sympatholytics; D009020:Morphine; D016627:Oxidopamine