Correlation Between Gut Microbiome Composition and Acute Pain Perception in Young Healthy Male Subjects.

OBJECTIVE: Recently, there has been growing interest in the gut-brain axis because it is emerging as a player influencing the health status of the host human. It is a known fact that the gut microbiome (GM) through the gut-brain axis has been implicated in numerous diseases. We previously reported that stool condition was associated with pain perception. Stool consistency and constipation are known to be associated with GM composition. Thus, we imagine that GM composition could influence pain perception. The aim of this study was to investigate the correlations between GM composition and pain perception and psychological states in young healthy male subjects. SUBJECTS: A total of 42 healthy young male volunteers completed the present study. METHODS: The volunteers' pain perceptions were assessed by pressure pain threshold, current perception threshold, temporal summation of pain, and conditioned pain modulation, and a questionnaire on psychological state was obtained. During the current perception threshold examination, we used 5, 250, and 2,000 Hz to stimulate C, Aδ, and Aß fibers. In addition, GM composition was evaluated by using 16S rRNA analysis. RESULTS: Pressure pain threshold showed a significant and negative correlation with Bacteroidetes phylum, in contrast to a significant and positive correlation with Firmicutes phylum. Current perception threshold of Aδ and Firmicutes phylum showed a significant correlation. There was a negative correlation between anxiety state and Bifidobacterium genus. In contrast, there was no significant correlation between psychological states and pain perceptions. CONCLUSION: The present study showed that acute pain perception was associated with GM composition in young healthy males.

Partner Loss in Monogamous Rodents: Modulation of Pain and Emotional Behavior in Male Prairie Voles.

OBJECTIVE: Pain is modulated by psychosocial factors, and social stress-induced hyperalgesia is a common clinical symptom in pain disorders. To provide a new animal model for studying social modulation of pain, we examined pain behaviors in monogamous prairie voles experiencing partner loss. METHODS: After cohabitation with novel females, males (n = 79) were divided into two groups on the basis of preference test scores. Half of the males of each group were separated from their partner (loss group), whereas the other half remained paired (paired group). Thus, males from both groups experienced social isolation. Open field tests, plantar tests, and formalin tests were then conducted on males to assess anxiety and pain-related behaviors. RESULTS: Loss males showing partner preferences (n = 20) displayed a significant increase in anxiety-related behavior in the open-field test (central area/total distance: 13.65% [1.58%] for paired versus 6.45% [0.87%] for loss; p < .001), a low threshold of thermal stimulus in the plantar test (withdrawal latencies: 9.69 [0.98] seconds for paired versus 6.15 [0.75] seconds for loss; p = .037), and exacerbated pain behaviors in the formalin test (total number of lifts: 40.33 [4.46] for paired versus 54.42 [1.91] for loss; p = .042) as compared with paired males (n = 20). Thermal thresholds in the plantar test significantly correlated with anxiety-related behavior in the open-field test (r = 0.64). No such differences were observed in the males that did not display partner preferences (r = 0.15). CONCLUSIONS: Results indicate that social bonds and their disruption, but not social housing without bonding followed by isolation, modulate pain and emotion in male prairie voles. The prairie vole is a useful model for exploring the neural mechanisms by which social relationships contribute to pain and nociceptive processing in humans.

Randomized open-label [corrected] non-inferiority trial of acetaminophen or loxoprofen for patients with acute low back pain.

BACKGROUND: Current worldwide clinical practice guidelines recommend acetaminophen as the first option for the treatment of acute low back pain. However, there is no concrete evidence regarding whether acetaminophen or nonsteroidal anti-inflammatory drugs (NSAIDs) is more effective for treating acute low back pain (LBP) in Japan. The present study aimed to investigate whether acetaminophen treatment for acute musculoskeletal pain was comparable with loxoprofen (a traditional NSAID in Japan) treatment. METHODS: Of the 140 patients with acute LBP who visited out-patient hospitals, 127 were considered eligible and were randomly allocated to a group taking acetaminophen or one taking loxoprofen. As primary outcome measure, pain intensity was measured using a 0-10-numeric rating scale (NRS). Moreover, pain disability, pain catastrophizing, anxiety, depression, and quality of life, as well as adverse events, were assessed as secondary outcomes. The primary outcome was tested with a noninferiority margin (0.84 on changes in pain-NRS), and the secondary outcomes were compared using conventional statistical methods at week 2 and week 4. RESULTS: Seventy patients completed the study (acetaminophen: 35, loxoprofen: 35). The dropout rates showed no significant difference between the two medication-groups. We found that the mean differences of changes in pain-NRS from baseline to week 2 or 4 between the two medication groups were not statistically beyond the noninferiority margin (mean [95% confidence interval]: -0.51 [-1.70, 0.67], at week 2 and -0.80 [-2.08, 0.48] at week 4). There were no consistent differences between the two medication groups in terms of secondary outcomes. CONCLUSIONS: The results suggest that acetaminophen has comparable analgesic effects on acute LBP, based on at least a noninferiority margin, compared with loxoprofen at 4 weeks. Acetaminophen seems to be a reasonable first-line option for patients with acute LBP in Japan.

Analysis of follow-up data from an outpatient pain management program for refractory chronic pain.

BACKGROUND: Numerous reports indicate that multifaceted pain management programs based on cognitive-behavioral principles are associated with clinically meaningful long-term improvements in chronic pain. However, this has not yet been investigated in Japan. This study investigated the effects of a multifaceted pain management program in Japanese patients with chronic pain, both immediately after the program and 6 months thereafter. METHODS: A total of 96 patients, 37 male and 59 female (mean age 63.8 years) experiencing treatment difficulties and suffering from intractable pain for more than 6 months were enrolled in the study. The programs were conducted with groups of 5-7 patients who met weekly for 9 weeks. Weekly sessions of approximately 2 h in duration incorporating a combination of lectures and exercise were conducted. Several measures related to pain and physical function were assessed at the start of the program, the end of the program, and 6 months after completion of the program. The resulting data were analyzed via Wilcoxon signed-rank test, and 'r' estimated by effect size was also assessed. RESULTS: Of the 96 initial participants, 11 dropped out during the program and 85 completed it. Thereafter, we evaluated 62 subjects at 6 months after the program, while 23 could not be evaluated at that time-point. Pain intensity upon moving, catastrophizing scores, and pain disability scores showed good improvements at the 6-month follow-up, with large efficacy (r > 0.5). Moving capacity and 6-min walking distance also showed good improvements with large efficacy, both at the end of the program and at the 6-month follow-up (r > 0.5). CONCLUSIONS: A multifaceted pain-management program based on cognitive-behavioral principles was effective in Japanese patients with chronic pain, resulting in improved long-term clinical outcomes.

Locomotive syndrome is associated not only with physical capacity but also degree of depression.

BACKGROUND: Reports of locomotive syndrome (LS) have recently been increasing. Although physical performance measures for LS have been well investigated to date, studies including psychiatric assessment are still scarce. Hence, the aim of this study was to investigate both physical and mental parameters in relation to presence and severity of LS using a 25-question geriatric locomotive function scale (GLFS-25) questionnaire. METHODS: 150 elderly people aged over 60 years who were members of our physical-fitness center and displayed well-being were enrolled in this study. Firstly, using the previously determined GLFS-25 cutoff value (=16 points), subjects were divided into two groups accordingly: an LS and non-LS group in order to compare each parameter (age, grip strength, timed-up-and-go test (TUG), one-leg standing with eye open, back muscle and leg muscle strength, degree of depression and cognitive impairment) between the groups using the Mann-Whitney U-test followed by multiple logistic regression analysis. Secondly, a multiple linear regression was conducted to determine which variables showed the strongest correlation with severity of LS. RESULTS: We confirmed 110 people for non-LS (73%) and 40 people for LS using the GLFS-25 cutoff value. Comparative analysis between LS and non-LS revealed significant differences in parameters in age, grip strength, TUG, one-leg standing, back muscle strength and degree of depression (p < 0.006, after Bonferroni correction). Multiple logistic regression revealed that functional decline in grip strength, TUG and one-leg standing and degree of depression were significantly associated with LS. On the other hand, we observed that the significant contributors towards the GLFS-25 score were TUG and degree of depression in multiple linear regression analysis. CONCLUSIONS: The results indicate that LS is associated with not only the capacity of physical performance but also the degree of depression although most participants fell under the criteria of LS.

Dorsal root ganglion pulsed radiofrequency for the management of intractable vertebral metastatic pain: a case series.

OBJECTIVE: Metastatic bone pain is characteristic of cancer pain and is a form of refractory cancer pain, as the pain includes not only nociceptive but also neuropathic pain. Although some drugs are effective in the management of painful bone metastases, pain while moving is one of the most refractory forms of pain. Although pulsed radiofrequency (RF) dramatically reduces neuropathic pain, chronic pain, and vertebral metastatic pain, the number of cases reported in these studies was very small (five or less). DESIGN: Case report. SETTING: Single pain center. PATIENTS: Fifteen patients suffering from intractable vertebral metastatic pain. INTERVENTIONS: Dorsal root ganglion (DRG) pulsed RF. OUTCOME MEASURES: A numerical rating scale (NRS) of pain at rest and while moving. RESULTS: Almost all patients experienced sound pain relief after the pulsed RF treatment. There were no severe side effects reported. CONCLUSION: DRG pulsed RF procedure provided sound pain relief for patients with intractable vertebral metastatic pain. Metastatic bone pain is characteristic of cancer pain and is a form of refractory cancer pain, as the pain includes not only nociceptive but also neuropathic pain. Although some drugs are effective in the management of painful bone metastases, pain while moving is one of the most refractory forms of pain. DRG pulsed RF procedure provided sound pain relief for patients with intractable vertebral metastatic pain.

Associations between pain drawing and psychological characteristics of different body region pains.

BACKGROUND: Pain drawings have frequently been used for documentation of pain and a convenient diagnosis tool. Pain drawings were found to be associated with psychological states in chronic patients with low back pain. Few researchers have investigated pain drawings except in low back pain. The aim of this study was to investigate the pain, pain drawings, psychological characteristics, and pain interference in the head, neck-shoulder (NS), and low-back/lower-limb (LB-LL) regions among patients with chronic pain. METHODS: We included a total of 291 patients with new chronic pain (headache, 62; NS pain, 87; LB-LL pain, 142). The pain drawings and scores of 10-cm Visual Analogue Scale (VAS), Hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), Short-Form McGill Pain Questionnaire (SF-MPQ), and Pain Disability Assessment Scale (PDAS) were extracted from medical records. A subset of 60 pain drawings was scored by senior and junior evaluators to assess inter-rater agreement. We investigated the correlation between pain drawings and VAS, HADS, PCS, SF-MPQ, and PDAS in each body region group at the initial visit. Moreover, almost all patients received nonsurgical treatment as a follow-up and were investigated using VAS after treatment. RESULTS: The reliability of pain drawings was substantial with an interevaluator reliability in headache, NS, and LB-LL pain. Nonorganic pain drawings were associated with psychological disturbances in NS and LB-LL pain, but not headache. Poor outcomes were associated with nonorganic drawings in LB-LL pain, but not in the case of headache or NS pain. CONCLUSIONS: Our results suggest that the characteristics of patients with nonorganic drawings differ according to body regions.

Predictive factors for the outcome of multidisciplinary treatments in chronic low back pain at the first multidisciplinary pain center of Japan.

[Purpose] Multidisciplinary treatments are recommended for treatment of chronic low back pain. The aim of this study was to show the associations among multidisciplinary treatment outcomes, pretreatment psychological factors, self-reported pain levels, and history of pain in chronic low back pain patients. [Subjects and Methods] A total of 221 chronic low back pain patients were chosen for the study. The pretreatment scores for the 10-cm Visual Analogue Scale, Hospital Anxiety and Depression Scale, Pain Catastrophizing Scale, Short-Form McGill Pain Questionnaire, Pain Disability Assessment Scale, pain drawings, and history of pain were collected. The patients were divided into two treatment outcome groups a year later: a good outcome group and a poor outcome group. [Results] One-hundred eighteen patients were allocated to the good outcome group. The scores for the Visual Analogue Scale, Pain Disability Assessment Scale, and affective subscale of the Short-Form McGill Pain Questionnaire and number of nonorganic pain drawings in the good outcome group were significantly lower than those in the poor outcome group. Duration of pain in the good outcome group was significantly shorter than in the poor outcome group. [Conclusion] These findings help better predict the efficacy of multidisciplinary treatments in chronic low back pain patients.

The effects of exercise therapy for the improvement of jaw movement and psychological intervention to reduce parafunctional activities on chronic pain in the craniocervical region.

PURPOSE: Apparent organic abnormalities are sometimes not identified among patients suffering from chronic pain in the craniocervical region. In some cases, parafunctional activities (PAs) are recognized. PAs are nonfunctional oromandibular activities that include jaw clenching and bruxism, but are considered as factors that contribute to craniomandibular disorders (CMDs). It is now recognized that PAs and CMDs influence musculoskeletal conditions of the upper quarter. Exercise therapy (ET) to improve jaw movement and psychological intervention (PI) to reduce PAs are useful for PAs and CMDs. We hypothesized that ET and PI would be effective for craniocervical pain without organic abnormalities. METHODS: Thirty-nine subjects suffering from craniocervical chronic pain were allocated into 3 groups: The control group received only pharmacological treatment; the ET group received jaw movement exercise (JME); and the ET-PI group received JME and PI. Pain and jaw movement were evaluated using a numerical rating scale (NRS). RESULTS: After interventions, the NRS scores were significantly lower in the ET-PI group, compared with those in the other groups. Jaw movement improved 100% in the ET group, 92% in the ET-PI group, and 0% in the control group. CONCLUSION: A combination of jaw exercise and psychological intervention to reduce parafunctional activities is more effective than jaw exercise alone for the improvement of craniocervical pain without apparent organic abnormalities.

Behavioral and neuropathological changes in animal models of chronic painful scar.

BACKGROUND: Long-lasting limb pain or back pain after surgery occasionally develops into chronic pain that leads to lower activity and a poorer quality of life for many patients. To determine the histopathological and neuropathological mechanisms that cause persistent post-operative pain, we developed an original animal model with sustained painful scars and then examined pain-related behavior and the pathological alteration of peripheral tissues and spinal nerves associated with the model. METHODS: The animal model (Scar group) was prepared in rats by extensively stripping subcutaneous tissue from the plantar in the hind paw followed by subsequent examination of pain-related behavior over the next 12 weeks. Thereafter, we conducted histological staining of the scar tissues, immunohistochemical staining of c-Fos (L5 dorsal horn), and electron microscopic analysis of the L5 spinal nerve fibers/dorsal roots. RESULTS: The mechanical pain threshold decreased specifically in the ipsilateral plantar in animals with scar. This state was maintained for 12 weeks. A collagen layer developed from fibers derma to the muscular layer in the scar tissue in which many fibroblasts were observed. No statistical differences were found for the areas of the c-Fos-immunoreactive (c-Fos-IR) neurons in the ipsilateral and contralateral sides of the L5 level of the dorsal horn in both the Scar group and Pinhole (sham operation) group. However, myelin sheath fragmentation of the nerve fibers was observed in the ipsilateral dorsal root at the L5 position. CONCLUSIONS: We created a persistent painful scar model through extensive injury of the peripheral tissues. Fibrotic thickening of the cutaneous tissues, possible sensitization, and partial degradation of the spinal nerve related to the painful scar were observed. This model should enable us to better understand the mechanism of sensitization caused by painful scar and investigate new methods for treating painful scars in humans.

Pulsed radiofrequency treatment within brachial plexus for the management of intractable neoplastic plexopathic pain.

We report on the use of pulsed radiofrequency (RF) within the plexus for the management of intractable pain in three patients with metastatic or invasive plexopathy. The patients were a 38-year-old woman with a history of breast cancer 6 years earlier whose computed tomography (CT) scans revealed a mass lesion at the infraclavicular part of the right brachial plexus, a 68-year-old man diagnosed with advanced lung cancer whose CT scans revealed a bone metastasis in the right humerus invading the axillary region of the right brachial plexus, and a 67-year-old woman diagnosed with advanced lung cancer whose CT scans revealed a bone metastasis in the left humerus invading the axillary region of the left brachial plexus. Ultrasound-guided pulsed RF was performed within the interscalene brachial plexus. During the follow-up period, their intractable pain was moderately controlled.

Intravenous lidocaine and magnesium for management of intractable trigeminal neuralgia: a case series of nine patients.

Most patients suffering from trigeminal neuralgia (TN) benefit from medical therapy, for example carbamazepin, gabapentin, and pregabalin, individually or in combination. Nonetheless, some patients experience severe and intractable pain despite such medication, or the medication eliminates their pain but they experience intolerable side effects sufficient to warrant discontinuation. Intravenous magnesium and lidocaine have been used for management of intractable neuropathic pain. We treated nine patients with TN by using an intravenous infusion of a combination of 1.2 g magnesium and 100 mg lidocaine for 1 hour, once a week for 3 weeks. All patients experienced sound pain relief after the combined intravenous infusion therapy. Two patients experienced short and mild dizziness after the therapy, but no severe side effects were reported.

The effect of celiac plexus block on heart rate variability.

BACKGROUND: Celiac plexus block (CPB) can be used for treating intra-abdominal visceral pain syndromes. The celiac plexus is the largest plexus of the sympathetic nervous system. Several nerve blocks have a marked effect on autonomic nervous activity. Furthermore, stellate ganglion block changes cardiac autonomic nervous activity. Thus, CPB could influence the sympathetic activity of the cardiac plexus. The aim of the present study was to see whether CPB modulated heart rate variability (HRV) in patients with pancreatic cancer. METHODS: Twelve patients received neurolytic CPB using 14 ml absolute alcohol. Data recorded in a palm-sized electrocardiographic unit were analyzed for HRV. RESULTS: CPB using a neurolytic solution did not induce any significant changes in the low-frequency (LF)/high-frequency (HF) ratio of HRV (LF/HF, P = 0.4642). Furthermore, the procedure did not induce any significant changes in blood pressure (systolic, P = 0.5051; diastolic, P = 0.5180). CONCLUSION: CPB did not induce any significant changes in HRV or hemodynamics.

Neurolytic celiac plexus block reduces occurrence and duration of terminal delirium in patients with pancreatic cancer.

PURPOSE: WHO's three step ladder sometimes cannot provide adequate pain relief for pancreatic cancer. Some patients develop terminal delirium (TD). The aim of this study was to test if the addition of a celiac plexus block (CPB) to pharmacotherapy could reduce the incidence of TD. METHODS: Pancreatic cancer patients under the care of our palliative-care team were investigated with regard to the duration and occurrence of TD, pain scores [numerical rating score (NRS)] and daily opioid dose. Between August 2007 to September 2008, 17 patients received only pharmacotherapy (control group). Then, we modified our guideline for analgesia, performing CPB 7 days after the first intervention of our team. Between October 2008 to September 2009, 19 patients received CPB. RESULTS: The opioid doses in CPB group were significantly lower both at 10 days after the first intervention (3 days after CPB) (27 ± 11 vs. 66 ± 82 mg; p = 0.029) and 2 days before death (37 ± 25 vs. 124 ± 117 mg; p = 0.009). NRS in the CPB group were significantly lower both at 10 days after the first intervention (0 [0-2] vs. 3 [2-5], p < 0.0001) and 2 days before death (1 [0-2] vs. 3 [1-4.5], p = 0.018). The occurrence and duration of TD in CPB group were both reduced (42 vs. 94 %, p = 0.019; and 1.8 ± 2.9 vs. 10.4 ± 7.5 days, p = 0.0003). CONCLUSION: The duration and occurrence of TD and the pain severity were significantly less in pancreatic cancer patients who underwent neurolytic CPB.

Associations between Degenerative Lumbar Scoliosis Structures and Pain Distribution in Adults with Chronic Low Back Pain.

BACKGROUND: This study aimed to investigate the location and distribution of pain in adults with chronic low back pain (LBP) with degenerative lumbar scoliosis (DLS) according to coronal deformities. METHODS: We enrolled 100 adults with chronic LBP and DLS, dividing them into two groups, a right-convex DLS group (n = 50) and a left-convex DLS group (n = 50). Dominant pain location was analyzed by dividing it into three parts-left side, right side, and center-and pain areas were identified using the pain drawing method; then, a heat map was created for each group. An association between pain location and convex side was analyzed as the primary outcome. Additionally, we assessed pain characteristics and radiological parameters, such as the curve structure and degree of degeneration. We used the Mann-Whitney U test or the chi-squared test to compare the clinical characteristics of the two groups, and generalized linear models were utilized to determine which variables were associated with pain severity or pain area. RESULTS: The results indicated that there was no significant difference between the two groups in terms of the association between the curve structure, pain severity and location. In multivariate analysis, although we did not find any variables associated with pain severity, we observed that age and a left-convex DLS were negatively correlated with pain area among all participants. The heat map demonstrated that individuals with chronic LBP frequently experienced pain in the central lumbar region, regardless of the coronal curve structure. CONCLUSIONS: Our findings suggest that degenerative coronal lumbar deformities may not have a specific pain pattern associated with a curved structure.

The Relationship between Numbness and Quality of Life.

BACKGROUND: Numbness is a term commonly used in clinical practice to describe an abnormal sensory experience that is produced by a stimulus or is present even without a stimulus. However, there is still much that remains obscure in this field, and also, few reports have focused on its symptoms. In addition, while pain itself is known to have a significant impact on quality of life (QOL), the relationship between numbness and QOL is often unclear. Therefore, we conducted an epidemiological survey and analyzed the relationship between painless numbness and QOL, using type, location, and age as influencing factors, respectively. METHODS: A nationwide epidemiological survey was conducted by mail using a survey panel designed by the Nippon Research Center. Questionnaires were sent to 10,000 randomly selected people aged 18 and over from all over Japan. Out of the 5682 people who responded, the relationship between numbness and QOL was analyzed using the EuroQol 5 Dimension-3L (EQ5D-3L) for patients who are currently experiencing painless numbness. FINDINGS: The results suggest that painless numbness affects QOL and that QOL decreases as its intensity increases. Furthermore, the two factors of numbness of feet and numbness among the young may be less likely to affect QOL. This study may be of great significance in the field of numbness research.

Transcutaneous Electrical Nerve Stimulation on the PC-5 and PC-6 Points Alleviated Hypotension after Epidural Anaesthesia, Depending on the Stimulus Frequency.

Neuraxial blockade causes arterial hypotension. Transcutaneous electrical nerve stimulation (TENS) at the Neiguan (PC-6) and Jianshi (PC-5) reduces the severity of hypotension after spinal anaesthesia, but did not clarify the optimal stimulus frequency. We hypothesized that the stimulus frequency of TENS at the PC-6 and PC-5 points would influence the severity of hypotension after epidural anaesthesia. 65 ASA I or II male patients presenting for inguinal hernia repair were randomized to five groups: the control group received no treatment; the 2 Hz, 10 Hz, 20 Hz, and 40 Hz groups received TENS at a frequency of 2 Hz, 10 Hz, 20 Hz, and 40 Hz, respectively. The lowest SBP was significantly higher in the 40 Hz group [the control, 84 (74-110) mmHg; the 2 Hz, 96 (62-116) mmHg; the 10 Hz, 100 (68-110) mmHg; the 20 Hz, 96 (64-115) mmHg; the 40 Hz, 104 (75-140) mmHg: P = 0.004]. Significantly less patients experienced hypotension in the 40 Hz group [the control, 78%; the 2 Hz, 43%; the 10 Hz, 38%; the 20 Hz, 38%; the 40 Hz, 8%: P = 0.008]. TENS on the PC-6 and PC-5 points reduced the severity and incidence of hypotension after epidural anaesthesia, depending on the stimulus frequency.