Differential Cortico-Thalamic reorganization in Opioid-Induced hyperalgesia and neuropathic pain male rats

Both opioid use and peripheral nerve injury can lead to hyperalgesia. Whereas in peripheral nerve injury, the central neuroplastic is secondary to sustained peripheral signaling, opioid-induced hyperalgesia (OIH) involves maladaptive alterations in both the peripheral and central nervous systems. However, the precise neurobiological mechanisms underlying these two distinct forms of hyperalgesia remain incompletely understood. In this study, OIH and spared nerve injury (SNI), a model of peripheral nerve injury, were established in male rats to investigate the similarities and differences in brain activity. Resting-state fMRI and mechanical stimulus task-state fMRI were employed to identify the differential brain regions between those two groups. Both resting-state fMRI and task-state fMRI revealed substantial differences in pain-related functional networks between these two models. Notably, OIH was characterized by a widespread reduction in whole-brain activity, whereas SNI primarily exhibited abnormal activation in specific pain-processing regions. Specifically, enhanced synchrony between the medial parietal association cortex (MPtA) and the ventral posterior thalamic nucleus (VP) was observed in the OIH model, but not in the SNI model. These abnormal changes were further confirmed through in vivo electrophysiological recordings. This study reveals a whole-brain activity responses to resting state and mechanical stimuli in both OIH and SNI models, while also identifying a special thalamo-parietal circuit involved in opioid-induced hyperalgesia. It provides new insights into the neural mechanisms between OIH and SNI, potentially guiding the new strategies for hyperalgesia therapy.