Effects of intrathecal antibodies to substance P, calcitonin gene-related peptide and galanin on repeated cold stress-induced hyperalgesia: comparison with carrageenan-induced hyperalgesia.
Rats exposed to a cold environment (4 degrees C) for 30 min every 1 h during the day and at night show a gradual decrease in the nociceptive threshold for pressure stimulation. Such hyperalgesia, referred to as repeated cold stress (RCS)-induced hyperalgesia, is stable for at least 4 h and maintained for 3 days only by exposing to cold overnight; thus, no adaptation to RCS is apparent. Hyperalgesia gradually returns over 4 days after cold exposure ceases. To determine whether three neuropeptides, substance P (SP), calcitonin gene-related peptide (CGRP) and galanin (GAL), which are present in the superficial dorsal horn including primary afferent terminals, would be responsible for RCS-induced hyperalgesia, we examined the effects of intrathecal injections of their antibodies (used as inhibitors of neuropeptide-mediated synaptic transmission) on the nociceptive threshold of RCS rats, and compared this with the antibody effect on carrageenan-induced hyperalgesia. An intrathecal injection of anti-SP antibody significantly inhibited the hyperalgesia of RCS rats as well as carrageenan-induced hyperalgesia, and slightly increased the nociceptive threshold of non-RCS rats. Anti-CGRP antibody produced an improvement in the hyperalgesia of RCS rats as well as carrageenan-induced hyperalgesia without having an effect on the nociceptive threshold of non-RCS rats. Although anti-GAL antibody significantly inhibited carrageenan-induced hyperalgesia, it did not affect the nociceptive threshold of RCS and non-RCS rats. The present results suggest that enhancement of synaptic transmission mediated by SP and CGRP, but not GAL, in the spinal dorsal horn is, at least in part, involved in RCS-induced hyperalgesia.
Satoh
Masamichi
M
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Kyoto University, Kyoto 606-01 Japan.
Kuraishi
Yasushi
Y
Kawamura
Minoru
M
D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000502:physiology*; D015740:Calcitonin Gene-Related Peptide / Q000276:immunology; D002351:Carrageenan; D003080:Cold Temperature / Q000009:adverse effects*; D019004:Galanin; D006930:Hyperalgesia / Q000139:chemically induced / Q000209:etiology*; D007278:Injections, Spinal; D008297:Male; D009479:Neuropeptides / Q000276:immunology*; D009619:Nociceptors / Q000502:physiology; D010146:Pain / Q000503:physiopathology; D010455:Peptides / Q000276:immunology; D051381:Rats; D011919:Rats, Inbred Strains; D012684:Sensory Thresholds; D013116:Spinal Cord / Q000502:physiology*; D013312:Stress, Physiological / Q000150:complications; D013373:Substance P / Q000276:immunology
D000906:Antibodies; D009479:Neuropeptides; D010455:Peptides; D013373:Substance P; D019004:Galanin; D002351:Carrageenan; D015740:Calcitonin Gene-Related Peptide