Central Neuropathic Pain Mechanisms and Management Post-Stroke

Central neuropathic pain following stroke arises when a cerebrovascular lesion disrupts sensory pathways in the central nervous system. Lesions in the thalamus, brainstem or somatosensory cortex lead to deafferentation and disinhibition of thalamocortical circuits, producing spontaneous dysaesthesia, mechanical allodynia and thermal hyperalgesia. At the spinal level, aberrant activation of dorsal horn neurones and loss of descending inhibitory control contribute to central sensitisation. Persistent microglial and astrocyte activation around lesion sites fosters a pro-nociceptive milieu, while maladaptive cortical reorganisation and interhemispheric imbalance further amplify pain perception. Management strategies combine pharmacological modulation of neuronal excitability with non-invasive neuromodulation and rehabilitative therapies. First-line medications typically include tricyclic antidepressants and sodium-channel blockers, while high-frequency repetitive transcranial magnetic stimulation, motor cortex stimulation and transcranial direct current stimulation aim to restore normal network dynamics. An integrated, personalised approach offers the best prospects for alleviating pain and optimising function in stroke survivors worldwide.

Research from Nature Portfolio

Recent animal studies have elucidated circuit-level mechanisms underlying post-stroke pain and the basis for neuromodulation-induced analgesia. In a non-human primate model, high-frequency repetitive transcranial magnetic stimulation applied to the primary motor cortex increased pain thresholds and enhanced tactile-evoked activity in motor and somatosensory regions, while reducing activity in the secondary somatosensory cortex, implicating an inhibitory system within this region in the relief of central post-stroke pain. A separate macaque study employing targeted lesions of the ventral posterolateral thalamic nucleus reproduced delayed mechanical allodynia and thermal hyperalgesia accompanied by long-lasting glial activation in perilesional tissue, providing a translational platform for testing novel therapeutic interventions aimed at modulating microglial and astrocyte responses.

Central Neuropathic Pain Mechanisms and Management Post-Stroke publication trend

The graph below shows the total number of articles in central neuropathic pain mechanisms and management post-stroke across all publications each year (not limited to Nature Index journals).

Technical terms

Allodynia: Pain elicited by stimuli that are normally non-painful.

Central sensitisation: Enhanced responsiveness of central neurones to sensory input, leading to pain amplification.

Deafferentation: Loss of sensory nerve input to the central nervous system due to lesion or injury.

Dysaesthesia: Unpleasant, abnormal sensations occurring spontaneously or in response to stimuli.

Hyperalgesia: Exaggerated pain response to stimuli that are normally painful.

Neuromodulation: Therapeutic alteration of nervous system activity through electrical or magnetic stimulation.

Repetitive transcranial magnetic stimulation (rTMS): A non-invasive technique delivering repeated magnetic pulses to modulate cortical excitability.

References

1. The role of spinal neurons targeted by corticospinal neurons in central poststroke neuropathic pain. CNS Neuroscience & Therapeutics (2024).
2. Stroke-Induced Central Pain: Overview of the Mechanisms, Management, and Emerging Targets of Central Post-Stroke Pain. Pharmaceuticals (2023).
3. Brain activity changes after high/low frequency stimulation in a nonhuman primate model of central post-stroke pain. Scientific Reports (2024).
4. Late-onset hypersensitivity after a lesion in the ventral posterolateral nucleus of the thalamus: A macaque model of central post-stroke pain. Scientific Reports (2017).
5. The mechanism and effect of repetitive transcranial magnetic stimulation for post-stroke pain. Frontiers in Molecular Neuroscience (2023).
6. Brain Stimulation Therapy for Central Post-Stroke Pain from a Perspective of Interhemispheric Neural Network Remodeling. Frontiers in Human Neuroscience (2016).