Spinal mu-opioid receptor-expressing dorsal horn neurons: role in nociception and morphine antinociception.
The role of spinal cord mu-opioid receptor (MOR)-expressing dorsal horn neurons in nociception and morphine analgesia is incompletely understood. Using intrathecal dermorphin-saporin (Derm-sap) to selectively destroy MOR-expressing dorsal horn neurons, we sought to determine the role of these neurons in (1) normal baseline reflex nocifensive responses to noxious thermal stimulation (hotplate, tail flick) and to persistent noxious chemical stimulation (formalin) and (2) the antinociceptive activity of intrathecal and systemic morphine in the same tests. Lumbar intrathecal Derm-sap (500 ng) produced (1) partial loss of lamina II MOR-expressing dorsal horn neurons, (2) no effect on MOR-expressing dorsal root ganglion neurons, and (3) no change in baseline tail-flick and hotplate reflex nocifensive responses. Derm-sap treatment attenuated the antinociceptive action of both intrathecal and systemic morphine on hotplate responses. Derm-sap treatment had two effects in the formalin test: (1) increased baseline nocifensive responding and (2) reduced antinociceptive action of systemic morphine. We conclude that MOR-expressing dorsal horn neurons (1) are not essential for determining nocifensive reflex responsiveness to noxious thermal stimuli, (2) are necessary for full antinociceptive action of morphine (intrathecal or systemic) in these tests, and (3) play a significant role in the endogenous modulation of reflex nocifensive responses to persistent pain in the formalin test. Thus, one would predict that altering the activity of MOR-expressing dorsal horn neurons would be antinociceptive and of interest in the search for new approaches to management of chronic pain.
Kline
Robert H
RH
Laboratory of Experimental Neurology, Tennessee Valley Healthcare System, Nashville, Tennessee 37212-2637, USA.
Wiley
Ronald G
RG
D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D008297:Male; D009020:Morphine / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D010147:Pain Measurement / Q000187:drug effects / Q000379:methods; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000819:agonists / Q000096:biosynthesis* / Q000235:genetics
D000700:Analgesics; D017450:Receptors, Opioid, mu; D009020:Morphine