Intrathecal CGRP(8-37) results in a bilateral increase in hindpaw withdrawal latency in rats with a unilateral thermal injury.
The present study was performed to explore the effects of intrathecal administration of calcitonin gene-related peptide8-37 (CGRP(8-37)) on the hindpaw withdrawal latency (HWL) to pressure in rats with one thermally injured hindpaw. Furthermore, the interaction of CGRP(8-37)and naloxone was studied. Thermal injury was performed by dipping the left paw into 60 degrees C for 20 s. This induced a significant increase in the volume of the left hindpaw (P<0.001) and significant bilateral decreases of the latency of hindpaw withdrawal response to mechanical stimulation (Left: P<0.001; right: P<0.05). Intrathecal administration of 10, 20 and 40 nmol of CGRP(8-37), but not of 1 or 5 nmol, induced a significant bilateral increase in HWLs (P<0.001). The effect of CGRP(8-37) was partly reversed by intrathecal injection of naloxone at a dose of 32 and 64 microg respectively. Using radioimmunoassay, we found a significant bilateral increase in the concentration of CGRP-like immunoreactivity in the perfusate of both hindpaws 24 h after unilateral thermal injury (left: P< 0.001; right: P< 0.05). There was also an increase in the amount of CGRP-like immunoreactivity in the cerebrospinal fluid (P< 0.001), but not in plasma. The results indicate that CGRP plays a role in the transmission of nociceptive information in the spinal cord of thermally injured rats. Furthermore, our findings suggest that opioids can modulate CGRP-related effects in the spinal cord.
Löfgren
O
O
Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.
Yu
L C
LC
Theodorsson
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Hansson
P
P
Lundeberg
T
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D000818:Animals; D000918:Antibody Specificity; D002056:Burns / Q000503:physiopathology*; D015740:Calcitonin Gene-Related Peptide / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000494:pharmacology*; D004487:Edema / Q000378:metabolism; D005110:Extracellular Space / Q000737:chemistry; D006358:Hot Temperature; D007249:Inflammation / Q000503:physiopathology; D007278:Injections, Spinal; D008297:Male; D008916:Miotics / Q000494:pharmacology*; D009270:Naloxone / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D010446:Peptide Fragments / Q000494:pharmacology*; D010812:Physical Stimulation; D011312:Pressure; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects*; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000737:chemistry / Q000502:physiology
D008916:Miotics; D009292:Narcotic Antagonists; D010446:Peptide Fragments; C058636:calcitonin gene-related peptide (8-37); D009270:Naloxone; D015740:Calcitonin Gene-Related Peptide