Refractory chronic headaches greatly impair the quality of life of migraine patients and also reduce social productivity. To elucidate the pathophysiology of the supersensitive brain state of refractory migraine attacks, and to discover the treatment and prophylaxis for the refractory chronic migraine, we analyzed a brain electric field under the light stimulation–induced brain supersensitivity. As a result, we found suppression of the cortical hyperexcitation only in patients with migraine without aura. This result suggested that the suppression of the cortical hyperexcitation by cortical spreading depression may have a role for inhibition of excitation in limbic system, vestibular system and the vomiting center. Next, cranial autonomic symptoms in patients with migraine have recently received attention. We showed that central sensitization, assessed by central sensitization inventory questionnaire, was more prevalent in migraine patients with cranial autonomic symptoms compared with those without cranial autonomic symptoms, suggesting a possible role of central sensitization in comorbid autonomic symptoms in migraine. Central sensitization is postulated to participate in not only severe pain but also in various symptoms such as fatigue, sleep disturbances, anxiety and depression in chronic pain syndrome. We believe our study results from migraine patients shed some light on the role of central sensitization in pathophysiology of chronic pain syndrome, but the elucidation of these relationships require further studies.
Physical inactivity or sedentary lifestyle is recognized as a risk factor for many diseases including cardiovascular disease, diabetes, cancer, depression, dementia and chronic pain, whereas physical exercise such as running, swimming and cycling is approved as an effective non–pharmacological intervention to improve pain. Many clinical and animal studies demonstrated that physical exercise significantly improves pain–related behaviors such as mechanical allodynia and heat hyperalgesia (exercise–induced hypoalgesia: EIH). Furthermore, multiple events including marked alterations in cytokines, neurotrophins, neurotransmitters and endogenous opioids in injured peripheral nerves, dorsal root ganglia, spinal dorsal horns and the brainstem following physical exercise have been proposed as potential mechanisms of EIH effects. On the other hand, neuroimaging analysis in chronic pain patients demonstrated that dysfunction of the mesocortico–limbic system including the ventral tegmental area (VTA), amygdala (Amyg), hippocampus (Hipp), nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) plays critical roles in the development and maintenance of chronic pain, which provided an important clue to elucidate novel mechanisms underlying EIH effects. Voluntary exercise (VE) in neuropathic pain (NPP) model mice significantly improved pain behaviors of these mice, and significant positive–correlation was observed between their total running distances and pain thresholds, suggesting that the increase of physical activity enhances analgesic levels. VE in NPP model mice significantly activated dopamine neurons in the lateral VTA, GABA neurons in the NAc lateral shell, glutamate (Glu) neurons in the medial basal Amyg and the deep layers of mPFC, whereas GABA neurons in the central nucleus of Amyg, Glu neurons in the lateral basal Amyg and GABA neurons in the superficial layers of mPFC were inhibited by VE. These changes may promote functional restoration of the mesocortico–limbic system leading to hypoalgesia and euphoria. Thus, the present review has shed light on the role of mesocortico–limbic system in the mechanisms underlying the EIH effects.
Operant methods that allow animals to avoid painful stimuli are interpreted to assess the aversive quality of pain, however, such measurements involve stimulation delivery by the experimenter and can induce fear, anxiety, or stress in animals, all of which can affect nociceptive threshold or mask pain behaviors. Here we developed a new operant method, the shuttle maze test, to assess the aversive quality of mechanical stimuli in rats after L5–L6 spinal nerve ligation (SNL) without externally applied stimuli by the experimenter. The shuttle maze test is based on the motivation for chocolate flavor cereal as a treat, and animals ambulates back and forth between two treat feeders by taking either a short route with a prickly–surfaced arch or a longer route with a smooth floor. The preference for taking the short route is a primary outcome measure of the test. Importantly, the animals do not have any painful consequences of not performing the task in the shuttle maze. SNL reduced the preference for the short route with the arch, correlated with hypersensitivity in the hindpaw. Oral gabapentin (30 and 100 mg/kg), pregabalin (100 mg/kg), and duloxetine (50 mg/kg) restored the short route preference and reduced hypersensitivity in SNL rats. These results suggest that SNL injury alters behavior in the shuttle maze test and that shuttle maze test shows comparable results to reflexive hypersensitivity after SNL in response to analgesics.
Objective: The goal of treating chronic pain is becoming more focused on improving ADL and QOL than on pain itself. In this study, we evaluated patients with central post–stroke pain (CPSP) by a multifaceted evaluation and examined factors related to ADL and QOL.
Methods: Patient background, stroke information, motor and sensory disturbance, pain site and duration, pain scales (VAS and Short–form McGill Pain Questionnaire 2; SF–MPQ2), Pain Catastrophizing Scale, Hospital Anxiety and Depression Scale (HADS), Pain Disability Assessment Scale (PDAS), EQ–5D–5L were obtained from 41 patients with CPSP. The factors related to PDAS and EQ–5D–5L were investigated by univariate and multivariate analyses.
Results: The univariate analysis showed that the PDAS was associated with motor disturbance scale (SIAS–motor: r=−0.67, p<0.01) and pain scales (VAS: r=0.32, p=0.04; SF–MPQ2: r=0.31; p=0.04), while the QOL value (EQ–5D–5L) was associated with motor disturbance scale (SIAS–motor: r=0.55, p<0.01), pain scales (SF–MPQ2: r=−0.54, p<0.01; VAS: r=−0.48, p<0.01), degree of sensory disturbance (p<0.01), and mood status (HADS depression item: r=−0.56, p<0.01; HADS anxiety item: r=−0.37, p<0.01). In multivariate analysis, the PDAS was largely affected by SIAS–motor and SF–MPQ2, and the QOL value was affected by multiple factors such as the SIAS–motor, SF–MPQ2, degree of sensory disturbance and HADS depression item.
Conclusions: The ADL and QOL in patients with CPSP reflect not only pain, but also motor and sensory impairments, and mood status, which should be noted when assessing.
Purpose: The aim of this study is to clarify the difference in influencing factors for chronic pain in each generation.
Method: There were 2,298 patients who visited Aichi Medical University Pain Center. The patient pedestrian score measured using iPad at the first visit was analyzed. Measurement items are Numerous Rating Scale (NRS), Pain Disability Assessment Scale (PDAS), Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), Pain Self–Efficacy Questionnaire (PSEQ), and Athens Insomnia Scale (AIS). For these items, average values were calculated for each age group of 10 years. Furthermore, linear regression was performed using NRS and PDAS as objective variables and other items as explanatory variables. A p value <0.05 was considered significant.
Result: NRS, PDAS and PCS were high after the 30s, HADS and AIS were high in the working generation, and PSEQ was low in the working generation. The number of patients is the lowest in teens and increased in the 40s, and there were many patients in the subsequent generations, with the largest number of men and women in their 60s. In the multiple regression analysis with NRS as the objective variable, AIS was selected with a significant difference in the generations excluding the 80s. In the 20s and 70s, PCS was selected. In the multiple regression analysis with PDAS as the objective variable, AIS was selected in the teens to 60s, PSEQ was selected in the 30s and over, and HADS depression was selected in the 40s and over.
Conclusion: We analyzed pain–related factors for each generation and found differences between generations. The working generation was worse in psychology and sleep than the other generations, and these affected pain symptoms.