To compare the efficacy and tolerability of adjunctive high frequency rTMS plus pregabalin over pregabalin alone in patients with CPSP: A randomized double- blind cross over trial in single-center tertiary care referral teaching hospital.

Stroke is the second leading cause of death in the world . Among those who survive, motor and somatosensory sequelae compromise the functional capacity and quality of life in many individuals. In general, one candefine two types of pain after stroke: pain associated with peripheral mechanisms (e.g., musculoskeletal, spastic pain, headache, and shoulder pain) and neuropathic central post-stroke pain (CPSP) CPSP can be disabling and further impactson quality of life, quality of sleep and has been associated with depression, fatigue, anxiety, difficulties in cognitive function and physical activity. Various pharmacotherapies are 1. Antidepressants- Amitriptyline includes (Balanced monoamine reuptake inhibition) 2. Anticonvulsants- a) Phenytoin (Voltage-gated sodium-channel blockade) b) Carbamazepine (Voltage-gated sodium-channel blockade) c) Lamotrigine (Presynaptic voltage-gated sodium-channel inhibition thus reduced release of presynaptic transmitters) d) Topiramate (Voltage-gated sodium-channel block and inhibition of glutamate release by an action on AMPA/kinase receptors) e) Gabapentin (Binding to α2δ subunit of presynaptic voltage-dependent calcium channels with reduced release of presynaptic transmitters) f) Zonisamide (Voltage-gated sodium-channel block) 3. Anesthetics – a) Lidocaine (Blockade of sodium channels thus preventing ectopic discharges) b) Mexiletine (Same as lidocaine) 4. NMDA receptor antagonist - Ketamine 5. Analgesics- Tramadol and morphine (μ opioid-receptor agonist and monoamine Morphine Reuptake inhibitor). Non--pharmacological treatment includes– 1. Invasive motor cortex simulation 2. Deep brain stimulation (DBS) 3. Repetitive transcranial magnetic stimulation (rTMS) 4. Vestibulocochlear stimulation has been tried in patients with CPSP refractory to pharmacotherapy. rTMS is a noninvasive technique that stimulates specific cerebral cortex regions by inducing electrical currents through coils placed on the cranium. M1 is a possible rTMS therapy target for neuropathic pain. Multiple studies have demonstrated that high-frequency (5–20 Hz) rTMS of the motor cortex alleviates chronic pain . rTMS has been an upcoming non- invasive, non-pharmalogical treatment modality for a number of neurological and psychiatric diseases including stroke recovery, migraine, fibromyalgia, movement disorders like Parkinson’s disease, essential tremors, Obsessive compulsive disorder, major depressive disorder etc. However, Level A evidence (definite efficacy) was reached for: high-frequency (HF) rTMS of the primary motor cortex (M1) contralateral to the painful side for neuropathic pain. Level B evidence (probable efficacy) was reached for: HF-rTMS of the left M1 or DLPFC for improving quality of life or pain, respectively, in fibromyalgia. Level A/B evidence is not reached concerning efficacy of rTMS in any other condition. The efficacy of Pregabalin in a RCT vs placebo was and the efficacy of rTMS v/s placebo in a RCT (Quesada et al) was 33.3%. However, there is paucity of information about comparing the efficacy of rTMS and pregabalin in the treatment of CPSP. Inthis context, we would like to conduct this prospective study to compare rTMS + pregabalin versus pregabalin alone in the treatment of CPSP.