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: Hypnotic analgesia is one of the most effective nonpharmacological methods for pain control. Hypnosis and distraction of attention from pain might share similar mechanisms by which brain responses to painful stimulation could be similarly reduced in both states. There is ample evidence for the efficacy of clinical hypnosis as a psychological intervention in the treatment of acute or chronic pain. Results are conflicting, however, with some studies showing an increase, others a reduction, and others still no change in the amplitude of event-related brain potentials during hypnosis as compared to control conditions. Here we compared the effects of clinical hypnosis to simple distraction of attention during recording of laser-evoked potentials (LEPs) in patients with chronic pain. Methods: The dominant hand in ten patients with chronic pain was tested with LEPs during: (I) resting state; (II) clinical hypnosis, and (III) distraction of attention. Nociceptive responses elicited by LEPs were graded on a numerical rating scale (NRS), and the change in N2-P2 complex amplitude during the three experimental conditions was analyzed. Results: N2-P2 amplitudes were significantly decreased during the hypnotic state as compared to the resting state and distraction of attention. Conclusions: Hypnosis is a modified state of consciousness that may differ from mental relaxation or distraction of attention from pain. A reduction in N2-P2 amplitude may result from the modulation of diverse brain networks, particularly the frontolimbic pathways, which could modify noxious stimuli input processing during hypnotic analgesia. Our findings indicate that several different brain mechanisms may act together in hypnosis and distraction of attention during pain processing and that clinical hypnosis may provide a useful non-invasive pain relief therapy.

Botulinum toxin (BT), a first-line treatment for focal dystonias in adults, has gained USA Food and Drug Administration approval for pediatric upper and lower extremity spasticity and sialorrhea, though its use in children younger than 2 years old is still considered off-label treatment for all pathologies. Dosing, treatment strategies and outcome measures lack international consensus, and they are often extrapolated from adult or spasticity guidelines. This review aims to evaluate the best available evidence on the efficacy and safety of BT therapy in pediatric dystonia (age under 21 years old), isolated or associated with other medical conditions. A comprehensive search in PubMed, Scopus and Web of Science was conducted, including only articles in English. Although no randomized controlled trials are still present, 12 articles were included with an overall of 57 patients. All the papers demonstrate that BT can improve motor function, decrease pain and ameliorate quality of life, with minimal adverse effects in pediatric patients affected by pure or mixed dystonic motor disorders. Despite the low level of evidence, our review shows that BT could be an efficacious treatment for these pediatric patients. The frequent generalized involvement, together with the heterogeneous nature of childhood dystonic forms, sometimes intermingled with spasticity, prompts further multicenter clinical trials or prospective studies with a higher level of evidence to shed light on the efficacy and safety profile of BT in pediatric dystonia.