Effects of motor imagery using virtual reality on pain sensitivity and affect in healthy individuals: A prospective randomized crossover study.

OBJECTIVE: Exercise induces a hypoalgesic response and improves affect. However, some individuals are unable to exercise for various reasons. Motor imagery, involving kinesthetic and visual imagery without physical movement, activates brain regions associated with these benefits and could be an alternative for those unable to exercise. Virtual reality also enhances motor imagery performance because of its illusion and embodiment. Therefore, we examined the effects of motor imagery combined with virtual reality on pain sensitivity and affect in healthy individuals. DESIGN: Randomized crossover study. SETTING: Laboratory. SUBJECTS: Thirty-six participants (women: 18) were included. METHODS: Each participant completed three 10-min experimental sessions, comprising actual exercise, motor imagery only, and motor imagery combined with virtual reality. Hypoalgesic responses and affective improvement were assessed using the pressure-pain threshold and the Positive and Negative Affect Schedule, respectively. RESULTS: All interventions significantly increased the pressure-pain threshold at the thigh (P<0.001). Motor imagery combined with virtual reality increased the pressure-pain threshold more than motor imagery alone, but the threshold was similar to that of actual exercise (both P≥0.05). All interventions significantly decreased the negative affect of the Positive and Negative Affect Schedule (all P<0.05). CONCLUSIONS: Motor imagery combined with virtual reality exerted hypoalgesic and affective-improvement effects similar to those of actual exercise.

Plasminogen activator inhibitor-1 is involved in glucocorticoid-induced decreases in angiogenesis during bone repair in mice.

INTRODUCTION: Glucocorticoids delay fracture healing and induce osteoporosis. Angiogenesis plays an important role in bone repair after bone injury. Plasminogen activator inhibitor-1 (PAI-1) is the principal inhibitor of plasminogen activators and an adipocytokine that regulates metabolism. However, the mechanisms by which glucocorticoids delay bone repair remain unclear. MATERIALS AND METHODS: Therefore, we herein investigated the roles of PAI-1 and angiogenesis in glucocorticoid-induced delays in bone repair after femoral bone injury using PAI-1-deficient female mice intraperitoneally administered dexamethasone (Dex). RESULTS: PAI-1 deficiency significantly attenuated Dex-induced decreases in the number of CD31-positive vessels at damaged sites 4 days after femoral bone injury in mice. PAI-1 deficiency also significantly ameliorated Dex-induced decreases in the number of CD31- and endomucin-positive type H vessels and CD31-positive- and endomucin-negative vessels at damaged sites 4 days after femoral bone injury. Moreover, PAI-1 deficiency significantly mitigated Dex-induced decreases in the expression of vascular endothelial growth factor as well as hypoxia inducible factor-1α, transforming growth factor-ß1, and bone morphogenetic protein-2 at damaged sites 4 days after femoral bone injury. CONCLUSION: The present results demonstrate that Dex-reduced angiogenesis at damaged sites during the early bone-repair phase after femoral bone injury partly through PAI-1 in mice.

Predictive Value of Pain Sensitization Associated with Response to Exercise Therapy in Patients with Knee Osteoarthritis: A Prospective Cohort Study.

Purpose: Knee osteoarthritis (KOA) is a degenerative disease with inflammation, becoming persistent as it progresses, resulting in reduced quality of life. Exercise is the recommended treatment for KOA; however, the extent of pain reduction with exercise is heterogeneous and the prognostic implications of baseline factors in patients undergoing exercise are still unknown. This study examined the association between the response to exercise therapy and clinical outcomes, radiologic severity, and pain sensitization, and investigated the optimal predictive value for the effectiveness of exercise. Patients and Methods: Demographics, radiologic severity, pressure pain threshold (PPT), and temporal summation of pain (TSP) at the knee, tibia, and forearm were assessed at baseline. The pain numeric rating scale (NRS) was assessed before and after 12 weeks of exercise. Patients were divided into responder/non-responder groups according to recommended criteria: responder, ≥30% reduction in pain; non-responder, <30% reduction in pain, and each variable was compared between the groups. The area under the curve (AUC) and cutoff points were determined by receiver operating characteristic curve analysis. Results: Sixty-five patients were categorized as responders and 26 as non-responders. In the non-responder group, baseline NRS (P<0.01), pain duration (P<0.01), and TSP at the knee (P<0.001) and tibia (P<0.05) were significantly higher, and PPT at the knee (P<0.001), tibia (P<0.001), and forearm (P<0.001) were significantly lower, than those in the responder group; however, no significant differences between groups were found in other demographics and radiologic severity. The variables that showed moderate or better predictive ability (AUC≥0.7) were PPT at the knee (cutoff points: 241.5 kPa), tibia (307.5 kPa), forearm (318.5 kPa), and TSP at the knee (15.5 mm). Conclusion: Our findings suggest that pain sensitization is associated with the response to exercise therapy. Furthermore, we provide clinically predictive values for PPT and TSP in predicting the outcome to exercise in KOA.

Effects of Exercise-Induced Hypoalgesia at Different Aerobic Exercise Intensities in Healthy Young Adults.

Purpose: Exercise-induced hypoalgesia (EIH) is a reduction in pain sensitivity that occurs following a single bout of exercise. However, little research has compared the EIH effects of exercise at different intensities, including low intensity, in the same participant. It is unclear as to which exercise intensities demonstrate EIH more effectively. The aim of this study was to examine and compare the effect of different intensities of exercise on pain sensitivity in the same participant. Methods: We included 73 healthy young adult volunteers (35 female and 38 male) in this experimental cross-over study. Each participant completed four experimental sessions of 30 min, consisting of aerobic exercise at 30% heart rate reserve (HRR), aerobic exercise at 50% HRR, aerobic exercise at 70% HRR, and quiet rest. EIH was assessed using the pressure pain threshold (PPT) and temporal summation of pain (TSP) in the quadriceps, biceps, and trapezius. Results: Low- and moderate-intensity exercise increased the multisegmental PPT and reduced TSP (all P < 0.05). High-intensity exercise increased the multisegmental PPT (all P < 0.05), but decreased TSP in only the quadriceps and biceps (P < 0.05), not the trapezius (P = 0.13). We found no difference in relative PPT and TSP changes between exercise intensities (P > 0.05) except for relative PPT change at the quadriceps (P < 0.05). Conclusion: Our results show that not only moderate- and high-intensity exercise, but also low-intensity exercise can produce a hypoalgesic response.

Pain Sensitization and Neuropathic Pain-like Symptoms Associated with Effectiveness of Exercise Therapy in Patients with Hip and Knee Osteoarthritis.

Pain sensitization and neuropathic pain-like symptoms are some of the common pain symptoms in patients with lower limbs, including hip and knee, osteoarthritis (HOA/KOA). Exercise therapy has been the first-line treatment; however, the effects differ for each patient. This prospective cohort study investigated the relationship between the effectiveness of exercise therapy and pretreatment characteristics (radiologic severity, pain sensitization, and neuropathic pain-like symptoms) of patients with HOA/KOA. We assessed the pain intensity using a numerical rating scale (NRS) before and after 12 weeks of exercise therapy in patients with HOA/KOA (n = 101). Before treatment, the Kellgren-Lawrence (K-L) grade; minimum joint space width (mJSW); pressure pain threshold (PPT) and temporal summation of pain (TSP) at the affected joint, tibia, and forearm; Central Sensitization Inventory-9; and painDETECT questionnaire (PDQ) were assessed. Cluster analysis was based on the pretreatment NRS and change in NRS with exercise therapy to identify the subgroups of pain reduction. The pretreatment characteristics of each cluster were compared. According to the results of the cluster analyses, patients in cluster 1 had severe pain that did not improve after exercise therapy, patients in cluster 2 had severe pain that improved, and those in cluster 3 had mild pain that improved. The patients in cluster 1 exhibited lower PPT at all measurement sites, higher TSP at the affected joint, and higher PDQ scores than those in other clusters. There was no difference in the K-L grade and mJSW among the clusters. The subgroup with severe pain and pain sensitization or neuropathic pain-like symptoms at pretreatment, even with mild joint deformity, may have difficulty in achieving improvement in pain after 12 weeks of exercise therapy. These findings could be useful for prognosis prediction and for planning exercise therapy and combining with other treatment.

Inhibition of current perception thresholds in A-delta and C fibers through somatosensory stimulation of the body surface.

Somatosensory stimulation of the body surface, such as through tactile and noxious stimulation, is widely known to inhibit pain. However, no studies have measured the threshold changes due to somatosensory stimulation of each nerve fiber (Aß, Aδ, and C) separately. We examined the changes in the current perception thresholds of Aδ, C, and Aß fibers induced by non-noxious and noxious somatosensory stimulation of the body surface. The current stimuli were sinusoidal waves at frequencies of 2000 Hz, 250 Hz, and 5 Hz, which selectively stimulated the Aß, Aδ, and C fibers, respectively. In the case of non-noxious stimulation, lightly rubbing the dorsal side of the forearm with a brush showed no significant physiological or clinical changes in the current perception thresholds of the Aδ, and C fibers; a significant increase was observed only in the Aß fibers. However, applying noxious stimulation to the body surface through hand immersion in cold water increased pain thresholds in both the Aδ and C fibers, and sensory threshold of the Aß fibers; changes in tactile thresholds were not significant. Inhibition of sensory information by nociceptive inputs may selectively suppress nociceptive stimuli.

Association of Chronic Pain with Radiologic Severity and Central Sensitization in Hip Osteoarthritis Patients.

PURPOSE: Pain and joint deformity are the most common symptoms of hip osteoarthritis (OA). However, no significant association between pain and severity of radiographic lesions has been reported. Recently, central sensitization has been suggested as an underlying mechanism of pain in OA. We investigated the involvement of radiologic severity or central sensitization in the clinical manifestation of hip OA with various degrees of joint deformity. PATIENTS AND METHODS: We included 39 patients with hip OA and divided them into two groups according to the severity of the hip pain: strong/severe (numerical rating scale, NRS≥6) and mild/moderate (NRS<6). We assessed the radiologic severity of OA using the Kellgren-Lawrence (K-L) scale and minimum joint space width (mJSW). We conducted quantitative sensory testing (QST) that included pressure pain threshold (PPT) and temporal summation of pain (TSP) at hip, tibialis anterior (leg), and extensor carpi radialis longus (arm) on the affected side. We examined the difference of radiologic assessment and QST results between each group and the correlation of the NRS with the radiologic assessment and QST results. RESULTS: There was no significant difference in the K-L scale and mJSW between patients with strong/severe and mild/moderate joint pain. Strong/severe pain patients demonstrated a lower PPT at all measurement sites and higher TSP at the hip and leg than the mild/moderate pain patients. In addition, NRS was significantly negatively correlated with PPT and positively correlated with TSP at all measurement sites, but not with the K-L scale and mJSW. CONCLUSION: We reported no significant difference in radiologic severity between patients with strong/severe and mild/moderate joint pain. By contrast, we found a significant difference in central sensitization represented by QST between strong/severe and mild/moderate joint pain groups. These results suggest that central sensitization may be involved in the joint pain of patients with hip OA who complain of severe pain despite less severe joint deformity.