Effect of medical cannabis on thermal quantitative measurements of pain in patients with Parkinson's disease.

BACKGROUND: Cannabis can alleviate pain of various etiologies. This study assessed the effect of cannabis on motor symptoms and pain parameters in patients with Parkinson's disease (PD). METHODS: Twenty patients with PD who were licensed to use cannabis underwent evaluation before and 30 min after cannabis consumption and again after long-term use. Motor function was assessed with the Unified PD Rating scale (UPDRS) by two raters, one blinded. Pain was assessed with the Pain Rating Index (PRI) and Visual Analogue Scale (VAS) of the short-form McGill Pain Questionnaire. Thermal quantitative sensory testing (QST) was performed in 18 patients. The two consecutive QST measurements were validated in 12 cannabis-naïve patients with PD. RESULTS: There was a significant decrease from baseline to 30 min after cannabis consumption in mean motor UPDRS score (38.1 ± 18 to 30.4 ± 15.6, p < 0.0001), total PRI (27 ± 13.5 to 9.7 ± 11, p = 0.001), and VAS score (6.4 ± 2.8 to 3.6 ± 3.1, p = 0.0005). Mean cold pain threshold decreased significantly in the more affected limb, but only after exclusion of two patients who consumed cannabis by vaporizer rather than smoking (19.5 ± 5.2 to 15.6 ± 8.7 °C, p = 0.02). After long-term (median 14 weeks) exposure, mean heat pain threshold decreased significantly in the more affected limb in all treated patients (43.6 ± 3.5 to 40.9 ± 3.3 °C, p = 0.05) and in cannabis smokers (43.7 ± 3.6 to 40.3 ± 2.5 °C, p = 0.008). CONCLUSIONS: Cannabis improved motor scores and pain symptoms in PD patients, together with a dissociate effect on heat and cold pain thresholds. Peripheral and central pathways are probably modulated by cannabis. SIGNIFICANCE: Quantitative sensory test results are significantly altered following cannabis consumption in patients with PD. Cannabis probably acts on pain in PD via peripheral and central pathways.

Contribution of genetic variants to pain susceptibility in Parkinson disease.

BACKGROUND: Pain is a one of the most disturbing non-motor symptoms of Parkinson disease (PD). The susceptibility to pain varies substantially among patients with PD. The aim of this study was to assess a potential association of genetic variants to PD-related pain. METHODS: We analysed 20 candidate SNPs from 12 genes previously reported to be associated with various pain phenotypes in a homogeneous group of 229 Israeli Jewish PD patients, with and without pain (n = 165 and 64, respectively). RESULTS: The statistical analysis accounted for the potential influence of demographic and clinical factors. The non-synonymous rs6746030 single nucleotide polymorphism (SNP) of the SCN9A gene, which alters the coding sequence of the sodium channel Nav1.7 (arginine to tryptophan), was nominally associated with PD-related pain susceptibility (p = 0.037), as well as with central and musculoskeletal pain subtypes independently. The synonymous rs324419 SNP of the FAAH gene which encodes fatty acid amide hydrolase, a cannabinoid metabolizing enzyme, was associated with PD-related pain (p = 0.006) and specifically with the musculoskeletal subtype. The FAAH haplotype of rs324419 and rs2295633 SNPs, which was previously associated with the variability in pain response in humans, was also associated with PD-related pain (p = 0.012) and specifically with PD-related musculoskeletal pain. CONCLUSIONS: Variants within in the SCN9A and FAAH genes were associated with the risk of pain in PD patients. These findings may contribute to our understanding of pain mechanisms of PD and to direct future therapies.