Not an Aspirin: No Evidence for Acute Anti-Nociception to Laser-Evoked Pain After Motor Cortex rTMS in Healthy Humans

No evidence of potentiation of buprenorphine by milnacipran in healthy subjects using a nociceptive test battery

“…In a recent review, Lotsch et al (2014) suggested that hyperalgesia and electrical pain models might be used to predict clinical analgesia in neuropathic pain. However, several pharmacological (NMDA receptor antagonists, tricyclic antidepressants, SNRIs, gabapentin) and non-pharmacological therapies (such as repetitive transcranial stimulation) that are used to treat neuropathic pain have shown contradictive results on acute pain models (Staahl et al, 2009b;Bradley et al, 2016). Therefore, although we were not able to show potentiation or synergy in these acute pain models, no conclusions can be drawn on a possible synergistic effect of milnacipran and buprenorphine in chronic pain conditions.…”

Can a single pulse transcranial magnetic stimulation targeted to the motor cortex interrupt pain processing?

“…We are the first to apply VL time-locked to M1 activity (VLM1) in relation to pain processing, however, similar intervention was already applied to other brain areas that have a role in different functions [ 21 , 37 , 38 , 68 – 70 ]. While some studies used time-locked single pulse TMS [ 20 ], other used pairs of TMS pulses [ 21 , 22 ] or a train of stimuli (rTMS) [ 28 , 71 ] in order to interfere with the cortical area’s function. This raises a question regarding the optimal TMS paradigm that is required for a VL.…”

“…Importantly, though not identical to VL, a recently published sham-controlled, double-blind cross-over study using HF-rTMS to M1 in healthy participants found no difference in pain intensity compared to sham [ 28 ]. In another supportive study, Borckardt et al (2011) employed different high and low frequency rTMS protocols to M1, on various experimental noxious stimuli including warm and cold sensory and pain threshold, as well as suprathreshold stimuli.…”

“…An experimental approach to study the functional contribution of a cortical area in a given task is 'Virtual lesion’ (VL), induced by applying brief transcranial magnetic stimulation (TMS) during a task performance [ 18 , 19 ]. VL can be achieved either by using a single or double TMS pulse [ 19 – 24 ] or by a short train of repetitive TMS (rTMS) [ 25 – 28 ] time locked to a stimulus or a task. The magnetic pulse operates as 'neural noise', adding random activity that interrupts the neural activity of the cortical region [ 29 – 32 ].…”

Frequency‐dependent top‐down modulation of temporal summation by anodal transcranial direct‐current stimulation of the primary motor cortex in healthy adults

“…This has been shown to be case for pharmacological agents such as ketamine, which has a greater effect during experimentally induced increased spinal cord excitability compared to acute testing (Arendt‐Nielsen et al., ). It may therefore be that noninvasive brain stimulation techniques are more effective during pathological pain states or when pain pathways become sensitized (Bradley et al., ).…”