REWIRING PAIN: INVESTIGATING THE ROLE OF THE CENTROLATERAL THALAMUS IN CHRONIC NEUROPATHIC PAIN

Chronic neuropathic pain (CNP), defined as pain initiated or caused by a primary lesion or disease of the nervous system, accounts for approximately 20–35% of all chronic pain cases and represents a severe, life-impairing condition often accompanied by affective comorbidities. Pharmacological treatments remain largely ineffective, motivating the exploration of alternative therapeutic strategies. Clinical evidence suggests that non-invasive ablation of the central lateral thalamic nucleus (CL), a medial thalamic region involved in bidirectional communication with the prefrontal cortex, may alleviate CNP symptoms, although the underlying mechanisms remain poorly understood.
Here, we confirm the beneficial effects of the ablation of CL neurons in a mouse model of CNP induced by chronic constriction injury (CCI). Behavioral analyses reveal a significant reduction in pain-related behaviors and suggest a role for the CL in modulating nociceptive and affective aspects of chronic pain.
To further characterize the central alterations associated with CNP, we examined brain-wide activity patterns in CCI mice compared to controls using whole-brain c-Fos mapping. Our analyses reveal widespread hyperactivity across multiple thalamic nuclei accompanied by cortical hypoactivity under CNP conditions. Consistently, patch-clamp recordings from CL neurons involved in thalamocortical processing demonstrate increased intrinsic excitability. Ongoing viral tracing experiments seek to determine whether these functional changes are associated with remodeling of thalamocortical functional connectivity at a whole-brain scale.