An important but not well-understood issue in pain research is the possibly different mechanisms of acute and chronic types of pain. Increasing evidence suggests that chronic pain is not simply the prolonged presence of acute pain (Banks and Watkins, 2006). The article by Ikeda et al.(2006) provides intriguing novel information about pain mechanisms in the amygdala in an animal model of chronic neuropathic pain (spinal nerve ligation model). These appear to be distinct from plastic changes in the amygdala observed at the more acute stage of arthritic pain (Neugebauer, 2006). The significance of the study by Ikeda et al.(2006) is twofold. The authors demonstrate synaptic plasticity and increased neuronal excitability in the amygdala in neuropathic pain using an identical approach to that described in the arthritis pain model (Neugebauer et al., 2003; Bird et al., 2005). The reproducibility of the previous findings clearly establishes the role of the amygdala in different types of pain. Even more importantly, though, the authors show that mechanisms of chronic neuropathic pain involve an N-methyl-D-aspartate (NMDA) receptor-independent form of plasticity in the amygdala, whereas increased NMDA receptor function is critical for plasticity associated with acute arthritic pain (Li and Neugebauer, 2004; Bird et al., 2005). Long known for its important role in emotional learning and behavior and affective disorders, the amygdala is particularly prone to neuroplastic changes (Maren, 2005; Phelps and Ledoux, 2005). Pain carries a negative affective valence and is intimately related to depression and anxiety disorders (Gallagher and Verma, 2004). Accumulating evidence suggests that the amygdala is an important neural substrate of the reciprocal relationship between pain and negative affect (Neugebauer, 2006). The amygdala comprises several anatomically and functionally distinct nuclei. The central nucleus of the amygdala (CeA) provides the output for major amygdala functions and modulates pain behavior through projections to descending pain control centers in the brainstem (Heinricher and McGaraughty, 1999; Neugebauer, 2006). The CeA receives purely nociceptive inputs from the dorsal horn via the parabrachial area (PB) and affect-related information from the circuitry of the lateral-basolateral amygdala (LA-BLA)(Neugebauer, 2006). These anatomically and functionally distinct lines of input at the PB-CeA and BLA-CeA synapses can be analyzed separately in brain slice preparations as shown in previous studies (Neugebauer et al., 2003) and confirmed by Ikeda et al.(2006). Despite the knowledge of nociceptive inputs to the amygdala, their functional significance in pain states was not known until a few years ago when synaptic plasticity and central sensitization in the CeA were demonstrated in a model of arthritic pain (Neugebauer and Li, 2003; Neugebauer et al., 2003). It remained unknown, however, if the changes that occurred within a few hours after arthritis induction would remain in chronic pain states or become extinct due to adaptive mechanisms. The study by Ikeda et al.(2006) is the first to show that neuroplastic changes in the amygdala persist in chronic neuropathic pain. In brain slices taken from animals one week after spinal nerve ligation, synaptic transmission at the PB-CeA and BLA-CeA synapses was enhanced compared to controls, indicating synaptic plasticity independent of peripheral or central sensitization outside the amygdala. Interestingly, synaptic transmission at the PB-CeA synapse was enhanced only contralateral to the site of peripheral nerve injury (in the right amygdala) whereas the bilateral increase of BLA-CeA …