Aim: Here, we investigated if MS-induced pain and bladder dysfunction can be attenuated by TRPV1 desensitization with RTX.
Introduction: Multiple sclerosis (MS) is the most prevalent neurological disorder in young people, causing irreversible disability and producing substantial economic and social impact. Among the most incapacitating symptoms, neuropathic pain and bladder dysfunction are reported by the majority of patients. The transient receptor potential vanilloid 1 (TRPV1) is a receptor described to have an important role in neuropathic pain, bladder dysfunction and inflammation. TRPV1 desensitization with agonists, such as resiniferatoxin (RTX), has been shown to improve bladder function and reduce behavioural signs of pain in various animal models of disease. In the context of MS, a recent study showed that TRPV1 knockout mice were protected from disease progressions, presenting delayed disease onset, myelin preservation and reduced clinical scores.
Methods: Experimental Auto-immune Encephalitis (EAE) was induced by a single injection in the flank of a solution of myelin basic protein (MBP) in Complete Freund's adjuvant (CFA). Behavioural tests were performed to evaluate symptoms. One month after MS-induction, animals were anesthetized and cystometries performed. Two other groups of MS animals received intrathecal RTX or vehicle and also submitted to behavioural tests and cystometries. At end of experiments, tissue was collected and processed.
Results: EAE rats developed neuropathic pain, as shown by the presence of mechanical allodynia and hypersensitivity to thermal stimuli. Cystometries performed at this time point showed signs of neurogenic detrusor overactivity. These clinical signs were accompanied by decreased spinal expression of MBP and increased activity of astrocytes and microglia. Preliminary observations suggest that intrathecal RTX improved cutaneous hypersensitivity and bladder function. These results suggest that TRPV1 might be involved in pain bladder dysfunction accompanying MS and that its modulation could have therapeutic relevance.
Conclusion: These results suggest that TRPV1 might be involved in pain bladder dysfunction accompanying MS and that its modulation could have therapeutic relevance.