The Efficacy Of Repetitive Transcranial Magnetic Stimulation(rTMS) For Patients With Postherpetic Neuralgia

BackgroundNeuropathic pain(Nep) is one of the most common and intractable chronic pain.Currently the mechanism of Nep is not fully understood, and there is lack of effective therapy. According to the damage location of the nervous system, Nep can be divided into central Nep and peripheral Nep. The latter includes Postherpetic Neuralgia(PHN),trigeminal Neuralgia, diabetic neuropathy pain and phantom limb pain. As a kind of typical peripheral Nep, PHN is the most common and severe complication of Herpes Zoster(HZ). Patients with PHN often suffer from mental and physical torment which significantly affects the quality of life.Transcranial Magnetic Stimulation(TMS), first proposed by Barker in 1985, is an electrophysiological technique using cortex stimulation to influence and change the brain function. The principle of TMS is based on Faraday law of electromagnetic induction.The magnetic pulses, produced by time-varying magnetic stimulator, noninvasively pass through the scalp and skull to the cerebral cortex. The magnetic pulses produce electric current to influence the action potential of cortex neurons, and change the plasticity of central nervous system, consequently, modify the brain metabolism.Transcranial magnetic stimulation is a noninvasive technique which is painless,convenient, safe and less side effects, and was previously used to treat some mental or neurological diseases. Recently, some clinical observations have reported that TMS may have short term analgesic effects on Trigeminal Neuralgia, suggesting that TMS may have potential effect on other kind of neuropathic pain.ObjectiveA prospective, randomized controlled clinical trial was designed to evaluate the safety and efficacy of repetitive transcranial magnetic stimulation(r TMS) for the treatment of PHN.MethodsPatients with PHN who suffered from acute herpes zoster for at least 1 month were enrolled and divided into three groups: no stimulation group(control group), real and sham r TMS stimulation groups. The treatment with r TMS was applied once a day for 15 days. VAS score was used to evaluate the pain relief and to adjust the dose of oral pregabalin. The follow-up duration was 3 months. The primary end point was Patients’ Global Impressions of Change(PGIC). The secondary end-points included VAS,SF-MPQ, the times of nerve block, and the dose change of oral pregabalin. The evaluation of clinical effect was assigned in two stages. The short-term evaluation was performed during the treatment period and 1 week after the treatment. The long-term evaluation was performed at the end of 1, 2, 3 months after treatment. Patients were randomly divided into three groups according to the registration order of patients. The patients voluntarily signed the informed consent. The patients were blinded to the assigned group during treatment.Fifty-one PHN patients were enrolled at the Pain Clinic of Xijing Hospital from January 2015 to January 2016. Forty-one patients completed the treatment and three months follow-up(17 in real r TMS stimulation group, 18 in control group, and 8 in sham r TMS stimulation group).Short-term Outcomes: At the end of the treatment and the 1st week follow up,PGIC(the number of patients who consider "significantly better") in the real stimulation group was significantly more than the control group(P1=0.0120) and sham stimulation group(P2=0.0400). The average VAS scores of three groups were significantly decreased,while the average VAS score of real stimulation group was statistically lower than the other two groups(P1=0.0080 and P2=0.0017). Furthermore, the number of patients whose VAS score decreased more than 2 cm in real stimulation group was significantly more than the other two groups(P1= 0.0080,P2=0.0020). Likewise, the SF-MPQ score of the real stimulation group was statistically better compared with the other groups(P1=0.0220 and P2=0.0485).Long-term Outcomes: At the end of three months follow up, PGIC(the number of patients who consider "significantly better") in the real stimulation group was significantly more than the other two groups(P1=0.0210,P2=0.0070). However, the average VAS score, the number of patients whose VAS score decreased more than 2 cm,the SF-MPQ score, the dose of oral pregabalin and times of nerve block had no statistically difference(P > 0.05) among the groups at the end of follow up.ResultsConclusionrTMS significantly attenuated pain and improved the life quality of PHN patients during the treatment period. Although this small sample RCT clinical trial suggested that r TMS is a safe and effective approach for PHN patients, large sample and multiple center trails are needed to conform the efficacy of r TMS therapy for PHN.