Cells and circuits for amygdala neuroplasticity in the transition to chronic pain

Maladaptive plasticity is linked to the chronification of diseases such as pain, but the transition from acute to chronic pain is not well understood mechanistically. Neuroplasticity in the central nucleus of the amygdala (CeA) has emerged as a mechanism for sensory and emotional-affective aspects of injury-induced pain, although evidence comes from studies conducted almost exclusively in acute pain conditions and agnostic to cell type specificity. Here, we report time-dependent changes in genetically distinct and projection-specific CeA neurons in neuropathic pain. Hyperexcitability of CRF projection neurons and synaptic plasticity of parabrachial (PB) input at the acute stage shifted to hyperexcitability without synaptic plasticity in non-CRF neurons at the chronic phase. Accordingly, chemogenetic inhibition of the PB→CeA pathway mitigated pain-related behaviors in acute, but not chronic, neuropathic pain. Cell-type-specific temporal changes in neuroplasticity provide neurobiological evidence for the clinical observation that chronic pain is not simply the prolonged persistence of acute pain. [Display omitted] •Synaptic plasticity at the PB→CeA pathway is lost in chronic neuropathic pain•Chemogenetic inhibition of the PB→CeA pathway inhibits acute but not chronic pain behaviors•CeA hyperexcitability shifts from CRF to non-CRF neurons at the chronic pain stage•CeA hyperexcitability no longer depends on PB→CeA synaptic plasticity in chronic pain The transition from acute to chronic pain and the chronification of diseases in general are not well understood mechanistically. Kiritoshi et al. demonstrate time- and cell-type-specific forms of neuroplasticity in chronic neuropathic pain in the amygdala, a brain region that is linked to the emotional-affective aspects of pain and pain modulation.