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Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis.

Abstract

Although clinical studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients' electrophysiological responses to noxious stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control. In a randomized, double-blind, placebo-controlled, cross-over study we investigated cannabinoid-induced changes in RIII reflex variables (threshold, latency and area) in a group of 18 patients with secondary progressive MS. To investigate whether cannabinoids act indirectly on the nociceptive reflex by modulating lower motoneuron excitability we also evaluated the H-reflex size after tibial nerve stimulation and calculated the H wave/M wave (H/M) ratio. Of the 18 patients recruited and randomized 17 completed the study. After patients used a commercial delta-9-tetrahydrocannabinol (THC) and cannabidiol mixture as an oromucosal spray the RIII reflex threshold increased and RIII reflex area decreased. The visual analogue scale score for pain also decreased, though not significantly. Conversely, the H/M ratio measured before patients received cannabinoids remained unchanged after therapy. In conclusion, the cannabinoid-induced changes in the RIII reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS.

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  • Authors+Show Affiliations

    ,

    Department of Neurological Sciences, University of Rome "Sapienza", Viale dell'Università 30, 00185 Rome, Italy.

    , , , , , , , , , , ,

    Source

    MeSH

    Administration, Oral
    Adult
    Afferent Pathways
    Analgesics
    Cannabinoids
    Central Nervous System
    Cross-Over Studies
    Double-Blind Method
    Dronabinol
    Female
    Humans
    Male
    Middle Aged
    Multiple Sclerosis, Chronic Progressive
    Neural Conduction
    Nociceptors
    Pain
    Pain Measurement
    Pain Threshold
    Placebos
    Reaction Time
    Reflex
    Treatment Outcome

    Pub Type(s)

    Journal Article
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    18603457

    Citation

    Conte, Antonella, et al. "Cannabinoid-induced Effects On the Nociceptive System: a Neurophysiological Study in Patients With Secondary Progressive Multiple Sclerosis." European Journal of Pain (London, England), vol. 13, no. 5, 2009, pp. 472-7.
    Conte A, Bettolo CM, Onesti E, et al. Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis. Eur J Pain. 2009;13(5):472-7.
    Conte, A., Bettolo, C. M., Onesti, E., Frasca, V., Iacovelli, E., Gilio, F., ... Inghilleri, M. (2009). Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis. European Journal of Pain (London, England), 13(5), pp. 472-7. doi:10.1016/j.ejpain.2008.05.014.
    Conte A, et al. Cannabinoid-induced Effects On the Nociceptive System: a Neurophysiological Study in Patients With Secondary Progressive Multiple Sclerosis. Eur J Pain. 2009;13(5):472-7. PubMed PMID: 18603457.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Cannabinoid-induced effects on the nociceptive system: a neurophysiological study in patients with secondary progressive multiple sclerosis. AU - Conte,Antonella, AU - Bettolo,Chiara Marini, AU - Onesti,Emanuela, AU - Frasca,Vittorio, AU - Iacovelli,Elisa, AU - Gilio,Francesca, AU - Giacomelli,Elena, AU - Gabriele,Maria, AU - Aragona,Massimiliano, AU - Tomassini,Valentina, AU - Pantano,Patrizia, AU - Pozzilli,Carlo, AU - Inghilleri,Maurizio, Y1 - 2008/07/07/ PY - 2008/01/16/received PY - 2008/05/22/revised PY - 2008/05/22/accepted PY - 2008/7/8/pubmed PY - 2009/7/16/medline PY - 2008/7/8/entrez SP - 472 EP - 7 JF - European journal of pain (London, England) JO - Eur J Pain VL - 13 IS - 5 N2 - Although clinical studies show that cannabinoids improve central pain in patients with multiple sclerosis (MS) neurophysiological studies are lacking to investigate whether they also suppress these patients' electrophysiological responses to noxious stimulation. The flexion reflex (FR) in humans is a widely used technique for assessing the pain threshold and for studying spinal and supraspinal pain pathways and the neurotransmitter system involved in pain control. In a randomized, double-blind, placebo-controlled, cross-over study we investigated cannabinoid-induced changes in RIII reflex variables (threshold, latency and area) in a group of 18 patients with secondary progressive MS. To investigate whether cannabinoids act indirectly on the nociceptive reflex by modulating lower motoneuron excitability we also evaluated the H-reflex size after tibial nerve stimulation and calculated the H wave/M wave (H/M) ratio. Of the 18 patients recruited and randomized 17 completed the study. After patients used a commercial delta-9-tetrahydrocannabinol (THC) and cannabidiol mixture as an oromucosal spray the RIII reflex threshold increased and RIII reflex area decreased. The visual analogue scale score for pain also decreased, though not significantly. Conversely, the H/M ratio measured before patients received cannabinoids remained unchanged after therapy. In conclusion, the cannabinoid-induced changes in the RIII reflex threshold and area in patients with MS provide objective neurophysiological evidence that cannabinoids modulate the nociceptive system in patients with MS. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/18603457/Cannabinoid_induced_effects_on_the_nociceptive_system:_a_neurophysiological_study_in_patients_with_secondary_progressive_multiple_sclerosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1090-3801(08)00129-8 DB - PRIME DP - Unbound Medicine ER -