1Institute for Biomedical Sciences of Pain, Tangdu Hospital, The Fourth Military Medical University, Xi’an 710038, China
2Key Laboratory of Brain Stress and Behavior, PLA, Xi’an 710038, China
3Nerve Injury and Repair Center, Beijing Institute for Brain Disorders, Beijing 100069, China
4Department of Pain Medicine, Guangzhou Red Cross Hospital, Guangzhou 510220, China
5Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children’s Hospital, Boston, MA, USA
6Department of Neurology, Boston Children’s Hospital, Boston, MA, USA
#These authors contributed equally to this work.

Abstract 

Intractable central post-stroke pain (CPSP) is one of the most common sequelae of stroke, but has been inadequately studied to date. In this study, we first determined the relationship between the lesion site and changes in mechanical or thermal pain sensitivity in a rat CPSP model with experimental thalamic hemorrhage produced by unilateral intra-thalamic collagenase IV (ITC) injection. Then, we evaluated the efficacy of gabapentin (GBP), an anticonvulsant that binds the voltage-gated Ca2+ channel α2δ and a commonly used anti-neuropathic pain medication. Histological case-by-case analysis showed that only lesions confined to the medial lemniscus and the ventroposterior lateral/medial nuclei of the thalamus and/or the posterior thalamic nucleus resulted in bilateral mechanical pain hypersensitivity. All of the animals displaying CPSP also had impaired motor coordination, while control rats with intra-thalamic saline developed no central pain or motor deficits. GBP had a dose-related anti-allodynic effect after a single administration (1, 10, or 100 mg/kg) on day 7 post-ITC, with significant effects lasting at least 5 h for the higher doses. However, repeated treatment, once a day for two weeks, resulted in complete loss of effectiveness (drug tolerance) at 10 mg/kg, while effectiveness remained at 100 mg/kg, although the time period of efficacious analgesia was reduced. In addition, GBP did not change the basal pain sensitivity and the motor impairment caused by the ITC lesion, suggesting selective action of GBP on the somatosensory system.

Keywords

central post-stroke pain; intracerebral hemorrhage; intra-thalamic collagenase injection; mechanical pain hypersensitivity; gabapentinoids; anti-allodynic effect

[SpringerLink]