How central is central poststroke pain? The role of afferent input in poststroke neuropathic pain: a prospective, open-label pilot study

Abstract

Central poststroke pain (CPSP) is a neuropathic pain disorder, the underlying mechanisms of which are not well understood. It has been suggested that stroke-associated loss of inhibitory neurons in the spinothalamic tract causes disinhibition of thalamic neurons, which autonomously generate ectopic nociceptive action potentials responsible for the pain experience. We hypothesized that CPSP is a result of misinterpretation of afferent sensory input by the sensitized neurons within the brain, rather than generated spontaneously by the damaged central nervous system (CNS) neurons. To test this hypothesis, we prospectively recruited 8 patients with definite CPSP affecting at least 1 extremity. In an open-label intervention, an ultrasound-guided peripheral nerve block with lidocaine was performed to block afferent sensory input from a painful extremity. Spontaneous and evoked pain, neuropathic pain descriptors, and lidocaine plasma concentrations were measured. The blockade of peripheral sensory input resulted in complete abolition of pain in 7 of the 8 subjects within 30 minutes (the primary outcome measure of the study), and >50% pain relief in the remaining participant. Median (interquartile range) spontaneous pain intensity changed from 6.5 (4.3-7.0) at baseline to 0 (0-0) after the block (P = 0.008). All mechanical/thermal hypersensitivity was abolished by the nerve block. The results suggest that it is unlikely that CPSP is autonomously generated within the CNS. Rather, this pain is dependent on afferent input from the painful region in the periphery, and may be mediated by misinterpretation of peripheral sensory input by sensitized neurons in the CNS.

Transcriptional Profiling of Non-injured Nociceptors After Spinal Cord Injury Reveals Diverse Molecular Changes

“…This has also been demonstrated in models of SCI by sustained spontaneous activity in peripheral terminals and in cell bodies of sensory neurons projecting to the skin after initial SCI (Carlton et al, 2009;Bedi et al, 2010;Wu et al, 2013;Yang et al, 2014;Ritter et al, 2015). Additional work has demonstrated that blockade of peripheral afferents into the central nervous system (CNS) can effectively mitigate patient discomfort and chronic pain (Campbell et al, 1988;Basbaum et al, 2009;Gold and Gebhart, 2010;Vaso et al, 2014;Haroutounian et al, 2018;Buch et al, 2019). These data support the idea that the mechanisms generating and maintaining prolonged pain reside within the peripheral nervous system.…”

Selective Nerve Fibre Activation in Patients with Generalized Chronic Pruritus: Hint for Central Sensitization?

“…Pruritic input from non-lesional skin might appear to be of minor pathophysiological importance; however, barrier impairment and xerosis is closely linked to systemic diseases leading to CP, such as renal failure (22), hepatobiliary conditions (23) or advance internal malignancies (24). Moreover, it is important to note that we have learned from patients with chronic pain that, even if the pathophysiology is restricted to the central nervous system, such as post-stroke pain, modulation of the peripheral input can still block ongoing pain (25). Thus, topical anti-pruritic treatment appears promising even if the main pathophysiological process is systemic.…”

Does Kinesiophobia Associated with Poststroke Neuropathic Pain and Stroke Severity?

“…Negative factors affecting the return of the patient can be listed as follows: low Bartel index score, long hospitalization, aphasia and previous alcohol use. [15][16][17] In our study, participants consisted of stroke patients in their 50s, about half of whom were in the acute phase. Most of them were in good condition according to the stroke severity scale as they were hospitalized for rehabilitation.…”