Pain in Multiple Sclerosis: Understanding Pathophysiology, Diagnosis, and Management Through Clinical Vignettes

Neuropathic pain and other pain syndromes occur in the vast majority of patients with multiple sclerosis at some time during their disease course. Pain can become chronic and paroxysmal. In this review, we will utilize clinical vignettes to describe various pain syndromes associated with multiple sclerosis and their pathophysiology. These syndromes vary from central neuropathic pain or Lhermitte's phenomenon associated with central nervous system lesions to trigeminal neuralgia and optic neuritis pain associated with nerve lesions. Muscular pain can also arise due to spasticity. In addition, we will discuss strategies utilized to help patients manage these symptoms.

The Effect of Cannabis-Based Medicine on Neuropathic Pain and Spasticity in Patients with Multiple Sclerosis and Spinal Cord Injury: Study Protocol of a National Multicenter Double-Blinded, Placebo-Controlled Trial

Disease or acquired damage to the central nervous system frequently causes disabling spasticity and central neuropathic pain (NP), both of which are frequent in multiple sclerosis (MS) and spinal cord injury (SCI). Patients with MS and SCI often request treatment with cannabis-based medicine (CBM). However, knowledge about effects, side effects, choice of active cannabinoids (Δ9-tetrahydrocannabinol (THC), cannabidiol (CBD) alone or in combination), and doses of CBM remains limited. Using a double-blind, parallel design in a national multicenter cohort, this study examines the effect of CBM on spasticity and NP. Patients are randomized to treatment with capsules containing either THC, CBD, THC and CBD, or placebo. Primary endpoints are patient-reported pain and spasticity on a numerical rating scale. Other endpoints include quality of life and sleep, depression and anxiety, and relief of pain and spasticity. Side-effects of CBM are described. In a sub-study, the pharmacodynamics (PD) and pharmacokinetics (PK) of oral capsule CBM are examined. We expect that the study will contribute to the literature by providing information on the effects and side-effects of CBD, THC, and the combination of the two for central neuropathic pain and spasticity. Furthermore, we will describe the PD/PK of THC and CBD in a patient population.

Markers of Central Neuropathic Pain in Higuchi Fractal Analysis of EEG Signals From People With Spinal Cord Injury

Central neuropathic pain (CNP) negatively impacts the quality of life in a large proportion of people with spinal cord injury (SCI). With no cure at present, it is crucial to improve our understanding of how CNP manifests, to develop diagnostic biomarkers for drug development, and to explore prognostic biomarkers for personalised therapy. Previous work has found early evidence of diagnostic and prognostic markers analysing Electroencephalogram (EEG) oscillatory features. In this paper, we explore whether non-linear non-oscillatory EEG features, specifically Higuchi Fractal Dimension (HFD), can be used as prognostic biomarkers to increase the repertoire of available analyses on the EEG of people with subacute SCI, where having both linear and non-linear features for classifying pain may ultimately lead to higher classification accuracy and an intrinsically transferable classifier. We focus on EEG recorded during imagined movement because of the known relation between the motor cortex over-activity and CNP. Analyses were performed on two existing datasets. The first dataset consists of EEG recordings from able-bodied participants (N = 10), participants with chronic SCI and chronic CNP (N = 10), and participants with chronic SCI and no CNP (N = 10). We tested for statistically significant differences in HFD across all pairs of groups using bootstrapping, and found significant differences between all pairs of groups at multiple electrode locations. The second dataset consists of EEG recordings from participants with subacute SCI and no CNP (N = 20). They were followed-up 6 months post recording to test for CNP, at which point (N = 10) participants had developed CNP and (N = 10) participants had not developed CNP. We tested for statistically significant differences in HFD between these two groups using bootstrapping and, encouragingly, also found significant differences at multiple electrode locations. Transferable machine learning classifiers achieved over 80% accuracy discriminating between groups of participants with chronic SCI based on only a single EEG channel as input. The most significant finding is that future and chronic CNP share common features and as a result, the same classifier can be used for both. This sheds new light on pain chronification by showing that frontal areas, involved in the affective aspects of pain and believed to be influenced by long-standing pain, are affected in a much earlier phase of pain development.

Pain quality of thermal grill illusion is similar to that of central neuropathic pain rather than peripheral neuropathic pain

Objectives Application of spatially interlaced innocuous warm and cool stimuli to the skin elicits illusory pain, known as the thermal grill illusion (TGI). This study aimed to discriminate the underlying mechanisms of central and peripheral neuropathic pain focusing on pain quality, which is considered to indicate the underlying mechanism(s) of pain. We compared pain qualities in central and peripheral neuropathic pain with reference to pain qualities of TGI-induced pain. Methods Experiment 1:137 healthy participants placed their hand on eight custom-built copper bars for 60 s and their pain quality was assessed by the McGill Pain Questionnaire. Experiment 2: Pain quality was evaluated in patients suffering from central and peripheral neuropathic pain (42 patients with spinal cord injury, 31 patients with stroke, 83 patients with trigeminal neuralgia and 131 patients with postherpetic neuralgia). Results Experiment 1: Two components of TGI-induced pain were found using principal component analysis: component 1 included aching, throbbing, heavy and burning pain, component 2 included itching, electrical-shock, numbness, and cold-freezing. Experiment 2: Multiple correspondence analysis (MCA) and cross tabulation analysis revealed specific pain qualities including aching, hot-burning, heavy, cold-freezing, numbness, and electrical-shock pain were associated with central neuropathic pain rather than peripheral neuropathic pain. Conclusions We found similar qualities between TGI-induced pain in healthy participants and central neuropathic pain rather than peripheral neuropathic pain. The mechanism of TGI is more similar to the mechanism of central neuropathic pain than that of neuropathic pain.