Prognosis of Pain after Stroke during Rehabilitation Depends on the Pain Quality.

OBJECTIVE: Pain after a stroke interferes with daily life and the rehabilitation process. This study aimed to clarify the prognosis of pain in subgroups of patients with pain after a stroke using pain quality data. METHODS: The study included 85 patients with pain after stroke undergoing exercise-based rehabilitation. Items of the Neuropathic Pain Symptom Inventory (NPSI) were used, and patients with pain after stroke were clustered according to their scores of NPSI. Other clinical assessments, such as physical and psychological conditions, were assessed by interviews and questionnaires, and then these were compared among subgroups in a cross-sectional analysis. Longitudinal pain intensity in each subgroup was recorded during 12 weeks after the stroke and the patients' pain prognoses were compared between subgroups. RESULTS: Four distinct subgroups were clustered: cluster 1 (cold-evoked pain and tingling), cluster 2 (tingling only), cluster 3 (pressure-evoked pain), and cluster 4 (deep muscle pain with a squeezing and pressure sensation). The cross-sectional analysis showed varying clinical symptoms among the subgroups, with differences in the prevalence of joint pain, limited range of motion, somatosensory dysfunction, and allodynia. There were no significant differences in pain intensity at baseline among the subgroups. A longitudinal analysis showed divergent prognoses of pain intensity among the subgroups. The pain intensity in cluster 4 was significantly alleviated, which suggested that musculoskeletal pain could be reduced with conventional exercise-based rehabilitation. However, the pain intensity of patients in clusters 1 and 2 remained over 12 weeks. CONCLUSION: The study classified patients into clinically meaningful subgroups using pain quality data and provided insight into their prognosis of pain. The findings could be useful for guiding personalized rehabilitation strategies for pain management. IMPACT: Assessment of pain quality in patients with pain after stroke leads to personalized rehabilitation for pain management.

Cortical oscillatory changes during thermal grill illusion.

OBJECTIVE: The thermal grill illusion (TGI) can cause a burning pain sensation when the skin is subjected to simultaneously harmless hot and cold stimuli, and the pain is reported to be similar to central neuropathic pain. Although electroencephalography (EEG) is commonly used in pain research, no reports have revealed EEG activity during TGI. METHODS: One healthy subject was enrolled, and EEG activity was recorded during the experience of the TGI and a warm sensation. Independent component analysis (ICA) was applied to preprocessed EEG data, which was divided into several clusters. RESULTS: Theta and alpha bands in the insular cortex and parietal operculum clusters were significantly more desynchronized under the TGI condition than under the warm condition ( P < 0.05). Additionally, theta, alpha and beta bands in the frontal (middle and inferior frontal gyrus) cluster showed significantly more desynchronization under the TGI condition than under the warm condition ( P < 0.05). CONCLUSION: EEG oscillations in these brain areas could be useful markers of central neuropathic pain.

Dietary vitamin B6 modulates the gene expression of myokines, Nrf2-related factors, myogenin and HSP60 in the skeletal muscle of rats.

Previous studies have suggested that vitamin B6 is an ergogenic factor. However, the role of dietary vitamin B6 in skeletal muscle has not been widely researched. The aim of the present study was to investigate the effects of dietary vitamin B6 on the gene expression of 19 myokines, 14 nuclear factor erythroid 2-related factor 2 (Nrf2)-regulated factors, 8 myogenesis-related factors and 4 heat shock proteins (HSPs), which may serve important roles in skeletal muscles. Rats were fed a diet containing 1 (marginal vitamin B6 deficiency), 7 (recommended dietary level) or 35 mg/kg of pyridoxine (PN) HCl/ for 6 weeks. Gene expressions were subsequently analysed using reverse transcription-quantitative polymerase chain reaction. Food intake and growth were unaffected by this dietary treatment. The rats in the 7 and 35 mg/kg PN HCl groups exhibited a significant increase in the concentration of pyridoxal 5'-phosphate in the gastrocnemius muscle compared with the 1 mg/kg PN HCl diet (P<0.01). The expressions of myokines, such as IL-7, IL-8, secreted protein acidic and rich in cysteine, IL-6, growth differentiation factor 11, myonectin, leukaemia inhibitory factor, apelin and retinoic acid receptor responder (tazarotene induced) 1, the expression of Nrf2 and its regulated factors, such as heme oxygenase 1, superoxide dismutase 2, glutathione peroxidase 1 and glutathione S-transferase, and the expression of myogenin and HSP60 were significantly elevated in the 7 mg/kg PN HCl group compared with the 1 mg/kg PN HCl diet (P<0.05). No significant differences in levels of these genes were observed between the 35 and 1 mg/kg PN HCl, with the exception of GDF11 and myonectin, whose expressions were significantly increased in the 35 mg/kg PN HCl (P<0.05). Notably, the majority of gene expressions that were affected responded to dietary supplemental vitamin B6 in a similar manner. The results suggest that compared with the marginal vitamin B6 deficiency, the recommended dietary intake of vitamin B6 upregulates the gene expression of a number of factors that promote the growth and repair of skeletal muscle.

Carnosine Content in Skeletal Muscle Is Dependent on Vitamin B6 Status in Rats.

Carnosine, a histidine-containing dipeptide, is well known to be associated with skeletal muscle performance. However, there is limited information on the effect of dietary micronutrients on muscle carnosine level. Pyridoxal 5'-phosphate (PLP), the active form of vitamin B6, is involved in amino acid metabolisms in the body as a cofactor. We hypothesized that enzymes involved in ß-alanine biosynthesis, the rate-limiting precursor of carnosine, may also be PLP dependent. Thus, we examined the effects of dietary vitamin B6 on the muscle carnosine content of rats. Male and female rats were fed a diet containing 1, 7, or 35 mg pyridoxine (PN) HCl/kg for 6 weeks. Carnosine in skeletal muscles was quantified by ultra-performance liquid chromatography coupled with tandem mass spectrometry. In the gastrocnemius muscle of male rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+70 and +61%, respectively) than in the 1 mg PN HCl/kg group, whereas that in the soleus muscle of male rats was significantly higher only in the 7 mg group (+43%) than in the 1 mg PN HCl/kg group (P < 0.05). In both muscles of female rats, carnosine concentration was significantly higher in the 7 and 35 mg groups (+32 to +226%) than in the 1 mg PN HCl/kg group (P < 0.05). We also found that, compared to the 1 mg group, ß-alanine concentrations in the 7 and 35 mg groups were markedly elevated in gastrocnemius muscles of male (+153 and +148%, respectively, P < 0.05) and female (+381 and +437%, respectively, P < 0.05) rats. Noteworthy, the concentrations of ornithine in the 7 and 35 mg groups were decreased in gastrocnemius muscles of male rats (-46 and -54%, respectively, P < 0.05), which strongly inversely correlated with ß-alanine concentration (r = -0.84, P < 0.01). In humans, 19% lower muscle carnosine content was found in soleus muscle of women of the lower plasma PLP tertile, but this was not observed in gastrocnemius muscle or in men. We conclude that adequate dietary vitamin B6 is essential for maintaining carnosine in skeletal muscles of rats. Significantly lower soleus carnosine content among women close to PLP deficiency suggests that a similar phenomenon exists in the humans.