OBJECTIVE:To determine a neuro-anatomic cause for central neuropathic pain (CNP) observed in multiple sclerosis (MS) patients.
METHODS:Parallel clinical and neuro-anatomical studies were performed. A clinical investigation of consecutively acquired MS patients with and without CNP (i.e. cold allodynia or deep hyperesthesia) within a single MS centre was pursued. The relationship between an upper central thoracic spinal cord focus to central pain complaints was examined. To identify the hypothesized autonomic interneurons with bilateral (both sides) descending projections to lumbosacral (Lower back) sensory neurons, retrograde (inject a tracer and it is taken down the nerve) single- and double-labeling experiments with fluorescent tracers were performed in three animal species (i.e. rat, cat, and monkey).
RESULTS:Clinical data were available in MS patients with (n = 32; F:23; median age: 34.6 years (interquartile range [IQR]: 27.4-45.5)) and without (n = 30; F:22; median age: 36.6 years [IQR: 31.6-47.1]) CNP. The value of a central focus between T1-T6 (Thoracic spine regions) in relation to CNP demonstrated a sensitivity of 96.9% (95% confidence interval [CI]: 83.8-99.9) and specificity of 83.3% (95% CI: 65.3-94.4). A significant relationship between CNP and a centrally located focus within the thoracic spine was also observed (odds ratio [OR]: 155.0 [95% CI lower limit: 16.0]; P < 0.0001).In all animal models, neurons with bilateral descending projections to the lumbosacral (lower back) superficial (surface) dorsal horn were concentrated in the autonomic intermediomedial nucleus surrounding the mid-thoracic central canal.
INTERPRETATION: Our observations provide the first evidence for the aetiology of CNP. These data may assist with the development of refined symptomatic therapies and allow for insights into unique pain syndromes observed in other demyelinating subtypes.
The autonomic nervous system (ANS), also known as the involuntary nervous system and is a division of the peripheral nervous system that functions as a control system (largely below the level of consciousness) over the function of internal organs. These functions include influencing heart rate, digestion, respiratory rate, salivation, perspiration,pupillary dilation, urination, sexual arousal, breathing and swallowing.
Within the brain, the autonomic nervous system is located in the medulla oblongata. Autonomic functions of the medulla include control of respiration, cardiac regulation (the cardiac control center), vasomotor activity (the vasomotor center), and certain reflex actions such as coughing, sneezing, swallowing and vomiting. Those are then subdivided into other areas and are also linked to ANS subsystems and nervous systems external to the brain. The hypothalamus, just above the brain stem, acts as an integrator for autonomic functions, receiving ANS regulatory input from the limbic system to do so.
The autonomic nervous system has two branches: the parasympathetic nervous system (PSNS), and the sympathetic nervous system (SNS). The sympathetic nervous system is often considered the “fight or flight” system, while the parasympathetic nervous system is often considered the “rest and digest” or “feed and breed” system. In many cases, PSNS and SNS have “opposite” actions where one system activates a physiological response and the other inhibits it. An older simplification of the sympathetic and parasympathetic nervous systems as “excitory” and “inhibitory” was overturned due to the many exceptions found. A more modern characterization is that the sympathetic nervous system is a “quick response mobilizing system” and the parasympathetic is a “more slowly activated dampening system”, but even this has exceptions, such as in sexual arousal and orgasm, wherein both play a role
Neuropathic pain is caused by damage or disease that affects the somatosensory system. It may be associated with abnormal sensations called dysesthesia, and pain from normally non-painful stimuli (allodynia). Neuropathic pain may have continuous and/or episodic (paroxysmal) components. The latter resemble an electric shocks. Common qualities include burning or coldness, “pins and needles” sensations, numbness and itching.