Shock-induced hyperalgesia: the role of the gaba and glutamate systems of the dorsolateral periaqueductal gray

Abstract

Exposure to moderate shock has been shown to sensitize subsequent pain. Following 3, 0.75 s, 1 my tailshocks, rats display lowered vocalization thresholds to radiant heat and a gradually incremented test shock (Illich, et al., 1995; King, et al., 1996). This shock-induced hyperalgesia, or enhancement in pain, can also be inferred by its ability to engender greater learning about a subsequent painful experience: a weak shock presented during this hyperalgesic state conditions greater fear to the context (King, et a1., 1996). Prior studies have concluded that the dorsolateral periaqueductal gray (dlPAG) is involved in this shock-induced hyperalgesia. Neurochemical lesions of the dlPAG eliminated both the decreases in vocalization thresholds to heat and shock, and the enhancement of learning, that are indicative of hyperalgesia (McLemore, et al, 1999). This study sought to determine the neurochemical system in the dlPAG involved in the induction of hyperalgesia. Chemically inactivating the dlPAG by microinjecting the GABA(A) agonist midazolam blocked shock-induced hyperalgesia (Experiment 1), providing evidence that the GABA system is involved in this process. However, indirectly activating the dlPAG by microinjecting the GABA antagonist bicuculline did not induce hyperalgesia. Instead, hypoalgesia was observed (Experiment 2). Hypoalgesia was also observed in response to direct activation with kainic acid of the dlPAG glutamatceptive neurons that are tonically inhibited by GABA (Experiment 3). This hypoalgesia was observed 2-20 min post-injection, a time frame similar to shock-induced hyperalgesia. However, at time points outside the timecourse of shock-induced hyperalgesia (35 and 50 min post-injection), hyperalgesia was observed on vocalization to heat and shock. Thus, activation of the same neurochemical system necessary for shock-induced hyperalgesia did not simply substitute for shock.