Locus coeruleus lesions in the rat enhance the antinociceptive potency of centrally administered clonidine but not morphine.
The nucleus locus coeruleus (LC) has been implicated in the descending inhibition of spinal nociceptive dorsal horn neurons, spinal nociceptive reflexes and in the antinociception produced by morphine. To further explore the involvement of the LC in antinociception, bilateral electrolytic lesions in the LC were made in adult male Sprague-Dawley rats. Lesions in the LC did not alter the antinociception produced by morphine (2.5 and 5 micrograms) administered in the periaqueductal gray in either the tail-flick (TF) or hot-plate (HP) tests when tested 7 and 14 days after the lesions. Baseline nociceptive thresholds in the TF and HP tests likewise were not affected at 7 or 14 days post-lesion. In contrast, the antinociceptive potency of clonidine administered intrathecally on day 13 post-lesion was enhanced significantly in the TF test; the antinociceptive ED50 of the LC lesion group was 0.52 micrograms whereas that of the sham lesion group was 2.29 micrograms. The antinociceptive potency of clonidine administered systemically (750 and 500 micrograms/kg, s.c.) was also enhanced in the LC lesion group in the TF but not the HP test. Norepinephrine (NE) in the lumbar spinal cord was correlated negatively and significantly with the extent of destruction of the LC. The lumbar spinal content of NE was reduced maximally at 12 days post-lesion (to 56% of control). The binding of [3H]clonidine in the lumbar spinal cord was slightly greater in the LC lesion than sham lesion group; the Bmax values were 42.4 fmol/mg protein and 35.5 fmol/mg protein for the LC lesion and sham lesion groups, respectively. It is suggested that the LC participates in the descending inhibition of spinal nociceptive transmission and that this inhibition may be mediated in the spinal cord by alpha-2 adrenoceptors located postsynaptically with respect to the NE terminals of the spinopetal LC efferents.
D000818:Animals; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D008125:Locus Coeruleus / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009638:Norepinephrine / Q000378:metabolism; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology*; D010487:Periaqueductal Gray / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology
D009020:Morphine; D003000:Clonidine; D009638:Norepinephrine