Background. Delta-9-tetrahydrocannabinol (THC)/cannabidiol (CBD) (nabiximols or Sativex^®) is an oromucosal spray formulation containing THC and CBD at an approximately 1:1 fixed ratio. Its administration for the treatment of pain in patients with multiple sclerosis (MS) has been established. MS patients generally complain of different kinds of pain, including spasticity-related and neuropathic pain. In this study, we compared and evaluated pain modulation and thermal/pain threshold of MS patients before and after THC/CBD administration. Methods. 19 MS patients underwent clinical examination, numerical rating scale (NRS), quantitative sensory testing (QST), and laser-evoked potentials (LEPs) before and after 1 month of therapy. Psychophysiological and neurophysiological data were compared to sex- and age-matched controls. Results. Patients reported a significant reduction in pain. We found statistically significant differences in LEP parameters between patients and controls but no significant change in LEP measures after THC/CBD therapy. Cold and heat detection thresholds were altered in patients but did not change after THC/CBD therapy. There was a significant increase in cold pain threshold by hand stimulation and a significant reduction in abnormal cold perception thresholds. Conclusions. Our results indicate that Sativex^® therapy provides pain relief in MS patients and suggest that it might modulate peripheral cold-sensitive TRP channels.

Background/Objectives: Tactile gnosis derives from the interplay between the hand’s tactile input and the memory systems of the brain. It is the prerequisite for complex hand functions. Impaired sensation leads to profound disability. Various invasive and non-invasive sensory substitution strategies for providing feedback from prostheses have been unsuccessful when translated to clinical practice, since they fail to match the feeling to genuine sensation of the somatosensory cortex. Methods: Herein, we describe a novel surgical technique for upper-limb-targeted sensory reinnervation (ulTSR) and report how single digital nerves selectively reinnervate the forearm skin and restore the spatial sensory capacity of single digits of the amputated hand in a case series of seven patients. We explore the interplay of the redirected residual digital nerves and the interpretation of sensory perception after reinnervation of the forearm skin in the somatosensory cortex by evaluating sensory nerve action potentials (SNAPs), somatosensory evoked potentials (SEPs), and amputation-associated pain qualities. Results: Digital nerves were rerouted and reliably reinnervated the forearm skin after hand amputation, leading to somatotopy and limb maps of the thumb and four individual fingers. SNAPs were obtained from the donor digital nerves after stimulating the recipient sensory nerves of the forearm. Matching SEPs were obtained after electrocutaneous stimulation of the reinnervated skin areas of the forearm where the thumb, index, and little fingers are perceived. Pain incidence was significantly reduced or even fully resolved. Conclusions: We propose that ulTSR can lead to higher acceptance of prosthetic hands and substantially reduce the incidence of phantom limb and neuroma pain. In addition, the spatial restoration of lost-hand sensing and the somatotopic reinnervation of the forearm skin may serve as a machine interface, allowing for genuine sensation and embodiment of the prosthetic hand without the need for complex neural coding adjustments.

We investigate the possibility to disrupt motor activity via premotor and parietal cortex stimulation, by inducing cortical silent periods (SPs) in the voluntarily activated upper limb. We analyzed data from 17 subjects with normal brain function, using navigated TMS (nTMS) on individual MR anatomies. We applied single-pulse biphasic stimulation at 120% of resting motor threshold (rMT) in blocks of 30 stimulations on each spot of a 10-16 point grid covering the inferior parietal and frontal lobes in the dominant hemisphere while participants performed voluntary submaximal contraction. Electromyography (EMG) was recorded bilaterally from intrinsic hand muscles. We observed SPs not preceded by a MEP in the contralateral hand in 16/17 participants. The maximum overlap, of individual areas where such MEP-independent SPs could be evoked, corresponded to the ventral precentral gyrus (MNI coordinates: [x=-57, y=7, z=33]). In a subset of stimulus sites, MEP-independent SPs were bilateral, with contralateral predominance. Canonical early-onset MEPs were observed in all patients, with maximum overlap over the primary motor cortex. We also observed rare contralateral late-onset (> 23 ms) MEP-like responses from peri-Rolandic TMS. MEP-independent SPs are systematically elicitable in healthy participants They likely reflect interference with premotor representations of ongoing movements. They offer a novel possibility to investigate higher-order motor functions in the experimental and clinical neurosciences.