Central Neuropathic Pain in Multiple Sclerosis is Associated with Impaired Innocuous Thermal Pathway



Central Neuropathic Pain in Multiple Sclerosis


Multiple sclerosis is a chronic disease in which inflammatory demyelinisation takes place in the central nervous system (Korn, 2008). An estimated three quarters of patients with MS suffer pain (Solaro, 2013). Pain can be secondary to other typical MS symptoms like spasticity or mood disorders, but may also be central neuropathic in its origin.


It is thus unclear whether central neuropathic pain (CNP) in MS originates from hyper-exitability of the pain system or from damage to the spino-thalamocortical (STTC) pathway. The STTC pathway conveys sensory information from noxious and thermal stimuli from the spinal cord to the thalamus and the cortex. Some of these inputs are also conveyed to the brainstem, such that indirectly, this pathway is also involved in descending inhibition.


Quantitative sensory testing (QST) may assist in discerning specific neural mechanisms from others. So far, there have been few pain physiology studies on MS patients, mostly using small patient cohorts and showing mixed results with QST. Some studies found that thermal sensory thresholds were impaired, which may point to damage to the STTC.


Other than thermal sensory thresholds, the Thermal Grill Illusion (TGI) may provide another clue on central mechanisms. During the TGI test innocious warm and cold stimuli are presented in parallel next to each other, which may cause a burning sensation, due to central interactions. Additionally, allodynia and hyperpatia are indicators of hyperexitability. Allodynia is a condition in which a non-painful stimulus is experienced as painful, while hyperpathia is defined as a painful syndrome characterized by an abnormally painful reaction to a stimulus, as well as an increased threshold ((IASP)., 1994).

Thus, Rivel (Rivel, 2021) and colleagues aimed to determine whether CNP among MS patients is associated with STTC function, pain pathways’ hyperexcitability ,or thermal grill illusion (TGI).


Sensory Testing


This study included 153 participants: 47 MS patients with CNP, 42 pain-free MS patients, and 36 healthy controls.

MS patients with CNP were tested on the most painful bodysite (for most on the shin, for some, the forearm), a comparable bodysite (e.g. contralateral bodysite or bodysite very close to it), and a painfree bodysite (volar forearm for most). Healthy controls and pain-free MS patients were tested on the shins and the mid-volar forearm.


Thermal testing included the measurement of warm sensation threshold (WST), cold sensation threshold (CST), and heat-pain threshold (HPT) as indicators of the STTC function. The scientists used Medoc’s Q-Sense CPM system to deliver heat and cold. The system has two thermodes with an active area of 30x 30 mm. The group also assessed the mechanical detection threshold (MDT) as an indicator of dorsal column-medial lemniscus pathway function. Hyperpathia was tested using the limits test in the warmth directionality. Static and dynamic mechanical allodynia were assessed using a thin Semmes-Weinstein monofilament and toothbrush, respectively. TGI was tested using two thermodes simultaneously with one increasing and the other decreasing in their temperature.


How patients with central neuropathic pain differ from those without


The experiments showed that patients with CNP had a higher warm sensation threshold (WST) in the painful leg compared with pain-free leg in the same group, and compared with non-CNP and healthy volunteers on the same bodysite. However, pain-free MS patients also differed significantly from HC in WST. The researchers observed a similar pattern in the hands.

Cold sensation threshold (CST) produced similar results. Patients with CNP had higher thresholds in the painful legs and hands compared with pain-free legs and hands in the same group and the other two groups. Pain-free MS patients also had higher thresholds than HC in CST.

The TGI heat and cold thresholds were significantly higher at the painful leg than the non-painful leg of CNP patients, and higher than those of the non-CNP patients and healthy controls.


Abnormal Sensations


Hyperpathia was higher in the painful legs and hands of CNP patients compared with the other groups. Interestingly, the more impaired the thermal threshold, the greater the prevalence of hyperpathia.


CNP characteristics and Sensory Profile


There were significant thermal sensory deificits in MS patients with CNP in both the legs and the arms, while for pain-free MS patients deficits were found only in the leg.

Of all the sensory variables, only a higher CST value was significantly associated with a greater prevalence of CNP.

The researchers also found that the greater the pain excitability, the greater the CNP severity and prevalence.

The authors concluded that CNP in MS is characterized by a specific impairment of STTC function and pain hyperexcitability. Thus, interventions to reduce excitability may mitigate CNP severity.


References


(IASP)., I. A. (1994). Classification of chronic pain: Description of chronic pain syndromes and definitions of pain terms (2nd ed.) . Seattle:: IASP.

Korn, T. (2008). Pathophysiology of multiple sclerosis. Journal of neurology, 2-6.

Rivel, M. A. (2021). Central neuropathic pain in multiple sclerosis is associated with impaired innocuous thermal pathways and neuronal hyperexcitability. Pain Medicine, 2311-2323.

Solaro, C. T. (2013). Pain and multiple sclerosis: pathophysiology and treatment. Current neurology and neuroscience reports, 1-9.

Medoc Ltd.