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. 2018 Jun 21;5(3):59.
doi: 10.3390/medicines5030059.

Pain Modulation after Oromucosal Cannabinoid Spray (SATIVEX®) in Patients with Multiple Sclerosis: A Study with Quantitative Sensory Testing and Laser-Evoked Potentials

Mara Turri  1 , Francesco Teatini  2 , Francesco Donato  3 , Giampietro Zanette  4 , Valeria Tugnoli  5 , Luciano Deotto  6 , Bruno Bonetti  7 , Giovanna Squintani  8
Affiliations

Pain Modulation after Oromucosal Cannabinoid Spray (SATIVEX®) in Patients with Multiple Sclerosis: A Study with Quantitative Sensory Testing and Laser-Evoked Potentials

Mara Turri et al. Medicines (Basel). .

Abstract

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.

Keywords: laser-evoked potentials; multiple sclerosis; oromucosal cannabinoid spray; pain; quantitative sensory testing.

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Conflict of interest statement

The authors declare no conflict of interest. The founding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, and in the decision to publish the results.

Figures

Figure 1
Figure 1
Laser-evoked potentials’ mean N2-P2 complex amplitudes for dominant hand and feet in control group (C) and patients before (PT0) and after (PT1) Sativex®. N2–P2 complex amplitudes in MS patients are significantly reduced in both dominant hand and feet compared to controls. No changes are observed after therapy. Amp: amplitude; *: statistically significant.
Figure 2
Figure 2
Laser-evoked potentials’ mean N2 latencies for dominant hand and feet in control group (C) and patients before (PT0) and after (PT1) Sativex®. N2 latencies in MS patients are significantly reduced in both dominant hand and feet compared to controls. No changes are observed after therapy. Lat: latency; *: statistically significant.
Figure 3
Figure 3
Quantitative Sensory Testing median values of cold and warm perception thresholds (CDT and HDT, respectively) and cold and heat pain thresholds (CPT and HPT, respectively) for hands and feet in control group (C) and patients before (PT0) and after (PT1) Sativex®. CDT and HDT for both hands and feet and HPT for feet are significantly altered in patients compared to controls and do not change after therapy. CPT measured by hand stimulation significantly rises after therapy. *: statistically significant.
Figure 4
Figure 4
Percentages of abnormal Quantitative Sensory Testing for hands and feet in patients before (PT0) and after (PT1) THC/CBD therapy. A significant reduction in abnormal cold detection threshold (CDT) after Sativex® is found in feet and a trend towards a reduction in abnormal CDT is also found in hands. *: statistically significant.
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