NMDA receptor-independent synaptic plasticity in the central amygdala in the rat model of neuropathic pain

Abstract

Neurons in the latero-capsular part of the central nucleus of the amygdala (CeA), a region now called the "nociceptive amygdala", receive predominantly nociceptive information from the dorsal horn through afferent pathways relayed at the nucleus parabrachialis (PB). Excitatory synaptic transmission between the PB afferents and these neurons is reported to become potentiated within a few hours of the establishment of arthritic or visceral pain, making it a possible mechanism linking chronic pain and unpleasant negative emotional experiences. However, it remains unknown whether such synaptic potentiation is consolidated or becomes adaptively extinct in the longer-lasting form of chronic pain, such as neuropathic pain, an as yet serious and frequent type of pain of important clinical concern. To address this issue, we recorded postsynaptic currents in CeA neurons evoked by PB tract stimulation in acute brain slices from young rats with neuropathic pain, as evaluated by tactile allodynic responses, following unilateral spinal nerve ligature made 1 week earlier. CeA neurons contralateral to the nerve ligation showed significantly larger-amplitude postsynaptic currents than those in the ipsilateral CeA and sham- and non-operated groups. The degree of synaptic potentiation, as compared between two sides, was positively correlated to that of tactile allodynia responses. In addition, blockade of NMDA receptors did not affect this potentiation. We conclude that potentiation of the PB-CeA synapse is consolidated in long-lasting neuropathic pain but that this potentiation results from a molecular mechanism distinct from that in arthritic and visceral pain.

Group III mGluR7 and mGluR8 in the amygdala differentially modulate nocifensive and affective pain behaviors

“…It is also important to consider that mGluR7 and mGluR8 may play different roles in more chronic pain states, because mechanisms of amygdala plasticity in acute and chronic pain models appear to be different (Ikeda et al, 2007;Neugebauer, 2007b). On the other hand, enhanced glutamatergic transmission is a key mechanism of amygdala plasticity in the acute (Bird et al, 2005; as well as the chronic pain model (Ikeda et al, 2007).…”

Role of Extracellular Signal-Regulated Kinase in Synaptic Transmission and Plasticity of a Nociceptive Input on Capsular Central Amygdaloid Neurons in Normal and Acid-Induced Muscle Pain Mice

“…In support of this argument, in vivo blockade of synaptic potentiation with intra-amygdaloid infusion of U0126 reduces behavior sensitization in mice with AIMP. This LTP-like enhancement might also account for the increased non-NMDAR-mediated currents at PBA-CeAC synapses seen in an arthritic pain model (Ikeda et al, 2007).…”

“…Furthermore, the potentiation of the aEPSC amplitude by PDA application was occluded in slices from AIMP mice. Accordingly, we propose that, in AIMP mice, an excessive nociceptive signal triggered by acidic saline injection into the gastrocnemius muscle activates ERK in the central amygdala, thereby enhancing PBA-CeAC synaptic transmission [see also Neugebauer et al (2003Neugebauer et al ( , 2004 and Ikeda et al (2007)]. Although the observation of increased pERK levels in the CeAC is consistent with previous studies, there is a substantial difference between the results of the present study and those of previous studies, in which mechanical hypersensitivity was shown to be functionally lateralized to the right amygdala in intraplantar formalin and arthritic models (Carrasquillo and Gereau, 2008;Ji and Neugebauer, 2009;Kolber et al, 2010).…”

“…In neuropathic and arthritic pain models, synaptic transmission of the PBA pathway on CeAC neurons (referred as to PBA-CeAC synapses) is enhanced (Neugebauer et al, 2003;Ikeda et al, 2007). However, whether such a change in efficacy of PBA-CeAC synapses is related to the reported elevation of ERK activity in the CeAC in animals with behavioral hypersensitivity (Carrasquillo and Gereau, 2007;Chen et al, 2010) remains unclear.…”

Central Sensitization and Descending Facilitation in Chronic Pain State

“…Supraspinal mechanisms: Contralateral effects may be mediated by brain activation and descending facilitation in chronic pain state. Persistent noxious inputs from the periphery may sensitize certain brain areas involved in the central pain circuitry, such as ACC, IC and amygdala (Ikeda et al, 2007) (for review, see Meeus & Nijs, 2007). Activation of these areas may cause bilateral hyperalgesia via descending pain control system (Fig.…”