PNB at the site contralateral to the injured hind paw did not result in CPP ( Fig. In contrast, in sham-operated animals or at 96 h postincision, when evoked hypersensitivity is still present, pairing PNB with the context did not produce CPP ( Fig. Peripheral nerve block (PNB) with popliteal fossa (PF) lidocaine injection given 24 h postincision resulted in strong preference for the chamber paired with PNB, demonstrating negative reinforcement. As demonstrated previously ( 22), evoked pain hypersensitivity was prominent at 24 h and still present, although diminished, at 96 h postincision.
#NEGATIVE REINFORCEMENT SKIN#
Incision of the skin and underlying hind-paw tissue induced time-dependent, observable pain behaviors, including guarding (avoidance of touching the floor with the injured area) and thermal hypersensitivity (decreased response latencies to a noxious thermal stimulus). It has been suggested that NAc neurons signal reward value and participate in behavioral decision making ( 17– 21). In vivo microdialysis measurements or fast-scan voltammetry demonstrate that appetitive rewards promote an efflux of dopamine in the NAc ( 15, 16). The NAc can be anatomically and functionally divided into core and shell regions that respectively receive projections from the lateral and medial VTA ( 14). Similarly, immunohistochemical studies show increased expression of the immediate early gene cFOS in the VTA in response to rewarding drugs, providing further support for an enhanced neuronal activity ( 10– 13). Electrophysiological recordings from dopaminergic neurons in the VTA demonstrate phasic neuronal activation by primary food or liquid rewards, by rewarding drugs, and reward-predicting cues ( 9). Manipulations that disrupt mesolimbic dopamine transmission attenuate food or drug reward-induced CPP ( 7, 8). Human functional imaging studies have shown that offset of an acute noxious stimulus ( 4, 5) or placebo analgesia ( 6) activates brain regions that overlap extensively with those implicated in appetitive rewards, in particular the ventral tegmental area (VTA), and its dopaminergic projections to the nucleus accumbens (NAc) ( 5, 6).