ANTIHYPERALGESIC EFFECTS OF SPINAL CANNABINOIDS

Cannabinoids have been widely reported to produce antinociception in m odels such as tail flick and hot plate. However, their role in modulat ing thermal hyperalgesia is unknown. The potency of some drugs, such a s the opioids, increases during hyperalgesia. Thus, we evaluated wheth er there is a change in the effectiveness of intrathecal cannabinoids with hyperalgesia. Additionally, we evaluated whether cannabinoids cou ld inhibit capsaicin-evoked neurosecretion from isolated rat spinal co rd. Our results indicate that 1 fmol anandamide (i.t.) completely bloc ked carrageenan-induced thermal hyperalgesia. However, anandamide at d oses as high as 100 pmol had no effect on thermal latencies in normal animals. Additionally, anandamide inhibited K+-as well as capsaicin-ev oked immunoreactive calcitonin gene-related peptide release. Finally, cannabinoid receptors were identified in sensory neurons. Collectively , these results indicate that there is an increased effectiveness of m odulation of thermal nociceptive thresholds by spinal cannabinoids dur ing hyperalgesia. This antihyperalgesic effect may be the result of ca nnabinoid-induced inhibition of neurosecretion from certain primary af ferent fibers. (C) 1998 Elsevier Science B.V.