Central Post-stroke Pain and Pharmacological Treatment: Work in Progress

Abstract

The International Association for the Study of Pain (IASP) defines central pain as “pain initiated or caused by a primary lesion or dysfunction of the central nervous system (CNS)” [1], at levels of spinal cord, brainstem or cerebral hemispheres. Central pain is less common in stroke than in other neurological diseases [2-4]. Central pain following stroke is a neuropathic chronic pain syndrome due to a post-stroke damage of CNS, resulting in anatomical, neurochemical, toxic, and inflammatory changes, causing an increase in neuronal excitability. Its frequency vary widely (8%–55%), reflecting small sample sizes, heterogeneous populations as well as differences in both study design, and chronic pain definition [3,5,6]. Central post-stroke pain can develops after both haemorrhagic and ischemic lesions occurring at any level of somato-sensory pathway of the brain, including medulla, thalamus, and cerebral cortex. Data from several studies indicate that the prevalence of central post-stroke pain is dependent on the location of the lesion, and occurrence is particularly high after lateral medullary infarction (or Wallenberg’s syndrome) or lesions in the ventroposterior thalamus [5]. Many of these patients will fulfil the diagnostic criteria for neuropathic pain, despite the pain being of nociceptive origin. In these cases, might be difficult to identify a central neuropathic element to the hemiplegic shoulder pain, spasticity, or other musculoskeletal pain and, in some cases, several pain types might be present in the same area of the body. The clinical manifestations of central post-stroke pain resemble those of other central and peripheral neuropathic pain syndromes [3,5]. There are no pathognomonic features or uniform signs with regard to onset, presentation, and intensity [5], and the characteristics and descriptions of central post-stroke pain vary substantially between patients. The presence of allodynia, hyperalgesia, or dysesthesia in response to the sensory examination is a predictor of central post-stroke pain [7]. The pathophysiology of central post-stroke pain is not well understood even if lack of central inhibition, imbalance of stimuli and central sensitization has been suggested. Moreover, a decrease of GABAergic inhibition has been observed at cortical, thalamic and spinal levels. Incomplete understanding of mechanisms underlying central post-stroke pain makes the development of targeted treatment demanding [3,5]. Moreover, the lack of published data from large and/or well-designed clinical trials involving patients with central post-stroke pain has created a situation where treatment guidelines are based upon “uncontrolled studies, clinical experience and expert opinion” [3].