Histamine-induced modulation of nociceptive responses.
Because previous studies suggest an antinociceptive role for the neuromodulator histamine (HA) in the periaqueductal grey or the nearby dorsal raphe (PAG/DR), a detailed pharmacological investigation of the effects of intracerebral HA on the hot-plate nociceptive test was performed in rats. Intracerebral microinjections of HA (1 microgram) into the PAG/DR or into the median raphe evoked a mild, reversible antinociceptive response; injections into lateral or dorsal midbrain evoked either a delayed response or no response, respectively. In the PAG/DR, the HA dose-response curve had an inverted U-shape, showing that HA can induce both antinociceptive (0.3-3 micrograms) and pro-nociceptive (10-30 micrograms) responses. Larger doses of HA (e.g., 100 micrograms) produced irreversible and highly variable antinociceptive responses that were accompanied by behavioral and histopathological changes; such effects, indicative of toxicity, were not observed after 0.3 microgram of HA, the peak antinociceptive dose. HA (0.3 microgram) antinociception was completely inhibited by intracerebral co-administration of the opiate antagonist naloxone (1 ng), the H1-receptor antagonist temelastine (20 pg), and the H2-receptor antagonist tiotidine (1 ng); none of these drugs altered nociceptive scores in the absence of HA. These results show that: (1) HA, a neurotransmitter in the PAG, can evoke antinociception in the absence of other behavioral or toxic effects; and (2) HA antinociception depends on the activation of both opiate and HA receptors in the PAG/DR.(ABSTRACT TRUNCATED AT 250 WORDS)
Thoburn
Kathleen K
KK
Department of Pharmacology and Toxicology, Albany Medical College (A-136), Albany, NY 12208 USA.
Hough
Lindsay B
LB
Nalwalk
Julia W
JW
Mischler
Scott A
SA
D000818:Animals; D002927:Cimetidine / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006632:Histamine / Q000008:administration & dosage / Q000494:pharmacology*; D006633:Histamine Antagonists / Q000494:pharmacology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D008297:Male; D008636:Mesencephalon; D008845:Microinjections; D009270:Naloxone / Q000494:pharmacology; D009619:Nociceptors / Q000187:drug effects*; D010147:Pain Measurement / Q000187:drug effects; D010487:Periaqueductal Gray / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D011744:Pyrimidinones / Q000494:pharmacology; D011903:Raphe Nuclei / Q000033:anatomy & histology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
D006633:Histamine Antagonists; D006634:Histamine H1 Antagonists; D006635:Histamine H2 Antagonists; D011744:Pyrimidinones; D009270:Naloxone; D002927:Cimetidine; D006632:Histamine; C049054:temelastine; C023990:tiotidine