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.