Cooperative mechanisms of neurotransmitter action in central nervous sensitization (original) (raw)

1996, Progress in brain research

During the past 5 years, our group has investigated the mechanisms of central sensitization of nociceptive pathways using 2 animal models: intradermal injection of capsaicin reviewed in Willis, 1994) and induction of acute arthritis Westlund, 1992, 1993a-d;; see review by . We have also explored the possibility of provoking sensitization more directly by administering drugs into the dorsal horn, either by iontophoresis or by microdialysis Dougherty et al., , 1995 Palecek et al., 1993a,b). Agents administered have included neurotransmitter agonists and antagonists, as well as drugs affecting second messenger systems. Central sensitization is characterized in our experiments by the following: (1) changes in the responses of primate spinothalamic tract (STT) neurons to stimulation of the skin, including increased responses to innocuous and marginally noxious stimuli and an enlarged receptive field; (2) behavioral responses to stimulation of the skin in rats indicative of allodynia and/or hyperalgesia; (3) morphological alterations in the dorsal horn in rats and monkeys; (4) and release of neurotransmitters into the dorsal horn, as determined by microdialysis and high performance liquid chromatography (HPLC) in rats and monkeys.