POST-STROKE PAIN: CARNOSINE MODULATION OF CENTRAL AND PERIPHERAL MECHANISMS

Stroke is a leading cause of disability, with 30% of ischaemic stroke patients developing post-stroke pain (PSP), a chronic neuropathic condition. The molecular and cellular mechanisms underlying PSP remain poorly understood and treatments are limited. Several pathways implicated in neuropathic pain and post-ischaemic injury may contribute to PSP, including calcitonin gene-related peptide (CGRP)-mediated nociceptive signalling, mitogen-activated protein kinase (MAPK) activation, sustained glial reactivity, and matrix metalloproteinase-9 (MMP9)-driven neuroinflammation. However, the involvement of these pathways in PSP has not yet been investigated. Carnosine, an endogenous dipeptide with neuroprotective properties, represents a potential therapeutic for modulating PSP. This study investigated neuropathic pain mechanisms in a mouse model of PSP and whether carnosine could modulate pain-associated molecular pathways. Male and female C57BL/6 mice underwent permanent ischaemia induced by distal occlusion of the left middle cerebral artery (pMCAO). Animals received carnosine or saline 2 hours post-injury. Dorsal root ganglion, spinal cord, and thalamic tissue were collected 28 days post-injury. Immunofluorescence analysis was performed using markers for CGRP, phosphorylated ERK (pERK), phosphorylated p38 (pP38), and GFAP. Imaging was conducted using a Leica DMi8 microscope and quantified with FIJI. Pain-related marker expression increased in contralateral peripheral and central nervous system tissues following pMCAO in vehicle-treated mice. Carnosine treatment attenuated the increased expression of pain-related markers in the contralateral peripheral and central nervous system tissue induced by stroke, indicating potential analgesic effects. These findings provide insight into pharmacological modulation of PSP and support MMPs-targeted strategies as potential therapeutic approaches to reduce PSP and improve recovery outcomes.