Increase In Pain Threshold Research Articles

Atorvastatin prevents the development of diabetic neuropathic nociception by possible involvement of nitrergic system.

Diabetic neuropathy has been identified as a common complication caused by diabetes. However, its pathophysiological mechanisms are not fully understood yet. Statins, also known as HMG-CoA reductase inhibitors, alleviate the production of cholesterol. Despite this cholesterol-reducing effect of statins, several reports have demonstrated their beneficial properties in neuropathic pain. In this study, we used streptozotocin (STZ)-induced diabetic model to investigate the possible role of nitric oxide (NO) in the antineuropathic-like effect of atorvastatin. Diabetes was induced by a single injection of STZ. Male rats orally received different doses of atorvastatin for 21 days. To access the neuropathy process, the thermal threshold of rats was assessed using hot plate and tail-flick tests. Moreover, sciatic motor nerve conduction velocity (MNCV) studies were performed. To assess the role of nitric oxide, N(G)-nitro-L-arginine methyl ester (L-NAME), aminoguanidine (AG), and 7-nitroindazole (7NI) were intraperitoneally administered along with some specific doses of atorvastatin. Atorvastatin significantly reduced the hyperalgesia in diabetic rats. L-NAME pretreatment with atorvastatin showed the antihyperalgesic effect, suggesting the possible involvement of the NO pathway in atorvastatin protective action. Furthermore, co-administration of atorvastatin with AG and 7NI resulted in a significant increase in pain threshold in diabetic rats. Our results reveal that the atorvastatin protective effect on diabetic neuropathy is mediated at least in a part via the nitric oxide system.

Changes in pain sensitivity and spinal stiffness in relation to responder status following spinal manipulative therapy in chronic low Back pain: a secondary explorative analysis of a randomized trial

BackgroundIn a prior randomized trial, we demonstrated that participants receiving spinal manipulative therapy at a pain-sensitive segment instead of a stiff segment experienced increased mechanical pressure pain thresholds. We hypothesized that the targeted segment mediated this increase through a segment-dependent neurophysiological reflective pathway. Presently, it is not known if this decrease in pain sensitivity is associated with clinical improvement. Therefore, we performed an explorative analysis to examine if changes in experimental pain sensitivity (mechanical and thermal) and lumbar stiffness were further dependent on clinical improvement in disability and patient-reported low back pain.MethodsThis study is a secondary explorative analysis of data from the randomized trial that compared 132 participants with chronic low back pain who received lumbar spinal manipulative therapy applied at either i) the stiffest segment or ii) the segment having the lowest pain threshold (i.e., the most pain-sensitive segment). We collected data at baseline, after the fourth session of spinal manipulation, and at 14-days follow-up. Participants were dichotomized into responders/non-responders using different clinical variables (disability and patient-reported low back pain) with varying threshold values (0, 30, and 50% improvement). Mixed models were used to assess changes in experimental outcomes (stiffness and pain sensitivity). The fixed interaction terms were time, segment allocation, and responder status.ResultsWe observed a significant increase in mechanical pressure pain thresholds for the group, which received spinal manipulative therapy at the most pain-sensitive segment independent of whether they improved clinically or not. Those who received spinal manipulation at the stiffest segment also demonstrated increased mechanical pain sensitivity, but only in the subgroup with clinical improvement. We did not observe any changes in lumbar stiffness.ConclusionOur results suggest the existence of two different mechanistic pathways associated with the spinal manipulation target. i) A decrease of mechanical pain sensitivity independent of clinical outcome (neurophysiological) and ii) a decrease as a reflection of the clinical outcome. Together, these observations may provide a novel framework that improves our understanding of why some respond to spinal manipulative therapy while others do not.Trial registrationClinicalTrials.gov identifier: NCT04086667 registered retrospectively September 11th 2019.

Chronic nanocurcumin treatment ameliorates pain-related behavior, improves spatial memory, and reduces hippocampal levels of IL-1β and TNFα in the chronic constriction injury model of neuropathic pain.

Memory deficit is a common cognitive comorbid in patients with neuropathic pain that need better treatment. Recent research revealed that nanocurcumin has an antinociceptive action and a protective effect against memory disorders, suggesting its possible effectiveness for the treatment of neuropathic pain and its comorbidity. Adult male albino Wistar rats (n = 32) were randomly divided into four experimental groups: CCI+ nanocurcumin, CCI + vehicle, sham + nanocurcumin, and sham + vehicle. Neuropathic pain induced by a chronic constriction injury of the sciatic nerve. Nanocurcumin or vehicle was injected intraperitoneally for 10days. Behavioral assessment achieved to evaluate pain threshold in the von Frey test and radiant heat test, also spatial learning and memory examined by the Morris water maze (MWM) test. To explore the possible relation, IL-1β, and TNF-α levels of the hippocampus measured by enzyme-linked immunosorbent assay (ELISA). Our data showed that CCI caused neuropathic pain-related behaviors and spatial learning and memory disorders in rats. Chronic treatment with nanocurcumin significantly increased pain threshold (P < 0.001; F = 27.63, F = 20.58), improved spatial memory (P < 0.01; F = 47.37), and decreased the hippocampal levels of IL-1β (P < 0.001; F = 33.57) and TNF-α (P < 0.01; F = 7.25) in CCI rats. Chronic nanocurcumin can ameliorate pain-related behavior, improve spatial learning and memory deficits, and is associated with the reduction of IL-1β and TNF-α levels in the hippocampus in CCI rats. Nanocurcumin may be potentially providing a therapeutic alternative for the treatment of neuropathic pain and its memory impairment comorbidity.

Old unsolved problems: when and how to treat silent ischaemia.

Silent myocardial ischaemia (SMI) is defined as objective evidence of ischaemia without angina (or equivalent symptoms) in the presence of coronary artery disease, differing from silent coronary artery disease. Silent myocardial ischaemia represents the majority of episodes of myocardial ischaemia at Holter monitoring. During transient myocardial ischaemia, the symptoms appear after the contraction anomalies of the left ventricle and after the ECG changes. The cause of silent myocardial ischaemia is still not well established. The severity and duration of ischaemia have been theorized as important elements in the SMI mechanism. Another possible mechanism responsible for SMI is represented by changes in the perception of painful stimuli with an increased pain threshold. Finally, a neuronal dysfunction of the diabetic, in post-infarction or a cardiac neuronal ‘stunning’ could play a role in SMI. In the pre-stent era, the SMI was associated with a worse prognosis. In patients with diabetes mellitus, SMI seems to be more represented because autonomic dysfunction is present in this category of patients. In conclusion, SMI is more frequent than symptomatic ischaemia. However, despite the presence of countless studies on the subject, it is not clear today whether medical therapy has equalized the risk and what the real prognosis of SMI is.

Magnesium Citrate Increases Pain Threshold and Reduces TLR4 Concentration in the Brain.

Magnesium is being investigated in various clinical conditions and has shown to be effective in some chronic pain models. However, it is not clear if oral magnesium use affects pain perception in acute pain. TLR4's (toll-like receptor) role in pain perception has emerged through its role in immune pathways and ion channels. The aim of this study is to investigate the effect of a single oral dose of magnesium citrate on pain conduction and whether with magnesium, the expression of TLR4 changes in the acute phase. Following a single dose of 66-mg/kg magnesium citrate administration to male Balb-c mice, pain perception (via hot-plate test), motor conduction (via electrophysiological recording, forelimb grip strength, rotarod and open-field tests), and emotional state (via elevated plus maze and forced swim test) were evaluated. In behavioral experiments, the control group was compared with applied magnesium for three different time groups (4, 8, 24 h). TLR4 expression was measured in four groups: control, magnesium (Mg), hot plate (HP), and Mg + HP. Hot plate latency was prolonged in the magnesium group (p < 0.0001) and electrophysiological recordings (p < 0.001) and forelimb grip strength measurement (p < 0.001) determined motor latency. Compared with the untreated hot plate group, TLR4 levels was lower in the brain (p = 0.023) and higher in the sciatic nerve (p = 0.001) in the magnesium-treated hot plate group. Consequently, the study indicated a single dose of magnesium citrate appeared to cause weakening in the transmission and perception of nociceptive pain. TLR4 may act as a regulator in magnesium's effects on pain perception.

Pain sensitivity and plasma beta-endorphin in adolescent non-suicidal self-injury

BackgroundBeta-endorphin (BE) has been suggested to play a central role as to why people engage in NSSI. To our knowledge, no study has systematically assessed this potential relationship in adolescents with NSSI. Methods94 adolescents with NSSI (according to DSM-5 criteria) and 35 healthy controls (HC) were enrolled. All participants received heat pain stimulation, with pain threshold and tolerance measured in °C. Plasma BE levels were assessed. Sociodemographic and clinical characteristics were obtained via semi-structured interviews and self-report questionnaires. ResultsAdolescents with NSSI showed increased pain thresholds (t(127)=2.071, p=.040), lower pain intensity (t(114)==2.122, p=.036) and lower plasma BE levels (t127==3.182, p=.002) compared to HC. Groups did not differ on pain tolerance (t(127)=0.911, p=.364). Greater pain threshold correlated positively with borderline personality disorder (BPD) symptoms (r=0.182, p=.039), while pain intensity (r=-0.206, p=.033) and BE levels (r=-0.246, p=.007) correlated negatively with depression severity. No significant relationship was found between pain threshold and plasma BE (r=-0.013, p=.882). LimitationsFuture studies should implement repeated plasma BE measures to assess BE release in association with pain in NSSI. Validity of plasma BE measures compared to central measures should be considered. Assessing the association between pain sensitivity (PS) and BE in a naturalistic setting presents a promising avenue for future research in NSSI. ConclusionsFindings support both reduced PS and basal opioid deficiency as independent biological correlates and potential risk-factors for NSSI. Further longitudinal and experimental studies are needed to investigate the role of BE levels and PS as well as their potential association.

Decreased Initial Peak Pain Sensation with Aging: A Psychophysical Study.

Background and PurposeAging is associated with an impairment of diverse physiological functions, including nociception. For example, older adults in comparison to young adults, show an overall increase in pain thresholds, reflecting a decline in pain sensitivity and changes in the nociceptive pathways. These results are, however, debated as they were not always replicated depending on the stimulus modality, duration, and location. The aim of the current study was to determine how the temporal evolution of pain intensity during a continuous tonic heat pain test is influenced by aging. More specifically, we wanted to 1) assess the effect of age on initial peak and late-phase pain and 2) determine whether potential age effects depend on the stimulation site.Participants and Methods13 young adults (average of 27.9 years old) and 13 older adults (average of 67.5 years old) participated in this study. Experimental heat pain was evoked on an appendicular (forearm) and axial (lower-back) body region, using a thermode (2-minute stimulation at a constant, individually-adjusted temperature). During the nociceptive stimulation, participants used a computerized visual analogue scale to continuously rate their pain.ResultsWe show that initial peak (0–30 seconds) pain sensation was significantly lower in older adults compared to young adults, while late-phase (30–120 seconds) pain sensation was similar across the two age groups. These results hold true for both stimulation sites, suggesting the existence of an age effect on both appendicular and axial body regions.ConclusionThe lower magnitude of initial peak pain observed in older adults, which affects both appendicular and axial body regions, could reflect generalized peripheral or central alterations of the nociceptive system in older adults. These alterations in older adults could have significant clinical impacts, such as an increased vulnerability to injury or an underestimation of the severity of their pain condition.

Pain perception and processing in individuals with posttraumatic stress disorder: a systematic review with meta-analysis.

Posttraumatic stress disorder (PTSD) is a known risk factor for the development of chronic pain conditions, and almost 1 in 5 individuals with chronic pain fulfills the criteria for PTSD. However, the relationship between PTSD and pain is poorly understood and studies on pain perception in patients with PTSD show inconsistent results suggesting that different sensory profiles exist among individuals with PTSD. Here, we (1) systematically summarize the current literature on experimentally evoked pain perception in patients with PTSD compared to subjects without PTSD, and (2) assess whether the nature of the traumatic event is associated with different patterns in pain perception. The main outcome measures were pain threshold, pain tolerance, and pain intensity ratings as well as measures of temporal summation of pain and conditioned pain modulation. A systematic search of MEDLINE, EMBASE, Web of Science, PsycINFO, and CINAHL identified 21 studies for the meta-analysis, including 422 individuals with PTSD and 496 PTSD-free controls. No main effect of PTSD on any outcome measure was found. However, stratification according to the nature of trauma revealed significant differences of small to medium effect sizes. Combat-related PTSD was associated with increased pain thresholds, whereas accident-related PTSD was associated with decreased pain thresholds. No clear relationship between PTSD and experimentally evoked pain perception exists. The type of trauma may affect pain thresholds differently indicating the presence of different subgroups with qualitative differences in pain processing.

Antinociceptive effects of lead acetate in sciatic nerve chronic constriction injury model of peripheral neuropathy in male Wistar rats.

The toxicological effects of lead and its compounds have overshadowed its possible health beneficial effects. Currently, the success rate for treating neuropathic pain has been very low. This study investigated the antinociceptive effects of orally administered low dose lead acetate in sciatic nerve ligated Wistar rats. Thirty Wistar rats randomly divided into five groups were used for this study. Chronic constriction injury (CCI) was used to induce neuropathic pain in Wistar rats. Allodynic and hyperalgesic signs were investigated using von Frey filaments and hotplate, respectively. Morris water maze test was used to assess the memory functions of the rats. The study revealed that oral administration of low-dose lead acetate significantly (p < 0.05) increased pain thresholds of ligated rats. CCI enhanced memory function in Wistar rats which was significantly decreased following lead acetate administration. The findings suggest that lead acetate possesses antinociceptive effects in peripherally induced neuropathic pain model in Wistar rats.

Exploring the Effect of Terminalia catappa Fruit Extract in Rheumatoid Arthritis: An Evaluation of Behavioural, Hematologiocal and Histopathological Parameters.

Rheumatoid Arthritis (RA) is an autoimmune disease characterized by failure of spontaneous resolution of inflammation with lifetime perseverance, becoming principal cause of inactivity. Many conventional therapies are in use but the side effects associated with them are equally problematic. Therefore, an urge to explore advanced therapeutic approaches with least adverse events has seeded the idea of discovering newer herbal drugs and their respective constituents in management of RA. The current research explores anti-arthritic activity of Terminalia catappa fruits hydroalcoholic extract in CFA induced Wistar rats. The fruits were obtained, washed, dried and processed to obtain hydroalcoholic powdered extract which was dissolved in water and given orally to the rats. Wistar rats of either sex were used in the study. The animals were injected with 0.1 ml of complete freund's adjuvant (CFA) in footpad of left hind paw. The treatment was initiated from day 0 by oral dosing of Terminalia catappa fruit extract in doses of 40 mg/kg and 80 mg/kg followed by CFA administration to day 21 and behavioral, hematological parameters besides histopathological screening were assessed simultaneously. The arthritic symptoms were observed to gradually decrease in treatment groups when compared against disease control groups. The parameters like body weight and pain latency were increased whereas paw volume and arthritic score were found to significantly decrease in treatment groups as compared to disease control group. The hematological parameters were also modified and were studied in treatment groups. The histopathological estimation depicted extent of damage in joint tissue of diseased rat comparable to normal, standard and combination therapy group. The fruits possess anti-arthritic properties and significantly reduced paw volume, arthritic score and increased pain threshold and body weight gain besides theory hematological effects like increase in Hb and RBC and decrease in WBC, platelets and ESR levels simultaneously. The histopathological estimation confirmed decreased deterioration of joint tissue in treatment groups as compared to disease control group hence proving to be an emerging therapeutic option in management of RA.

Synthesis and Evaluation of a Series of New Bulleyaconitine A Derivatives as Analgesics.

As a nonaddictive analgesic widely used in clinics, the LD50 of bulleyaconitine A is just only 0.92 mg/kg, which exhibits obvious toxicity. Therefore, 31 new non-natural C19-diterpenoid alkaloids (2a–w, 2′a–e, 3, 4a, and 4b) were designed and synthesized from bulleyaconitine A to develop nonaddictive analgesics with low toxicity. The chemical structures were characterized by 1H NMR, 13C NMR, and high-resolution mass spectrometry (HRMS) spectra. The analgesic activities were evaluated by a hot plate test in mice. At the dosage of 10 mg/kg, six compounds (2d, 2j, 2k, 2m, 2t, 2w) exhibited good analgesic activities (increased pain threshold >100%) with a long duration. Among them, 2w showed the best analgesic activity and the longest duration. Its pain threshold reached 166.35% in 15 min, peaked at 30 min (182.35%), and remained 82.59% even at 60 min.

Prenatal pregabalin is associated with sex-dependent alterations in some behavioral parameters in valproic acid-induced autism in rat offspring.

This study was performed to evaluate the effects of prenatal exposure to pregabalin (PGB) on behavioral changes of rat offspring in an animal model of valproic acid (VPA)-induced autism-like symptoms. Pregnant rats received VPA (600mg/kg/i.p.) once at 12.5 gestational days for autism-like symptom induction in offspring. After the delivery single male and single female offspring from each mother were randomly selected for behavioral test (anxiety, pain response, pleasure, and motor function) at 60th day adulthood (n=7). Offspring received prenatal PGB (15 & 30mg/kg/i.p.) during gestational days 9.5 to 15.5 either alone or in combination with VPA (PGB15, PGB30, PGB15+VPA, and PGB30+VPA). Control offspring received normal saline during the same period. The result showed that prenatal VPA exposure was associated with autism-like behaviors in rat offspring. PGB treatment during the gestational period revealed significant reduction in sucrose preference test and anxiety in elevated plus maze and open field test in offspring. Also, PGB treatments exhibited a dose-dependent increase in pain threshold in prenatally VPA exposed rats in tail-flick and hot plate test. Also, there was a sex-related significant impairment in motor function in beam balance and open field test, and male rats were affected more than females. However, no significant sex differences in sucrose preference and pain sensitivity were observed in prenatal PGB-treated rat offspring. In conclusion, prenatal exposure to VPA increased the risk of autism-like behaviors in the offspring rats, and PGB treatment during the gestational period was associated with some beneficial effects, including anxiety reduction and motor impairment in autism-like symptoms in rat offspring.

Imagined and Actual Acupuncture Effects on Chronic Low Back Pain: A Preliminary Study.

Background Research suggests that imagined experiences can produce brain responses similar to those produced by actual experiences. Shared brain responses that support both imagination and perception may underlie the functional nature of mental imagery. In a previous study, we combined acupuncture and imagery to develop a new treatment method, video-guided acupuncture imagery treatment (VGAIT). We found that VGAIT significantly increased pain thresholds in healthy subjects. The aim of this study is to extend our previous finding by investigating whether VGAIT can relieve symptoms in patients with chronic low back pain. Methods We first performed a single-arm study in which we administered video-guided acupuncture imagery treatment (VGAIT) on patients with chronic low back pain (cLBP) (Study 1, n = 18, 12 females). We then compared our findings to those from a recently published study in which real or sham acupuncture treatment was applied on patients with cLBP (Study 2, n = 50, 31 females) using a similar protocol. All patients in Studies 1 and 2 received 6 treatments over 4 weeks. Results All three treatments (VGAIT, real, and sham acupuncture) significantly reduced pain severity as measured by a low back pain bothersomeness score. VGAIT produced similar effects to real acupuncture (p = 0.97) and nonsignificantly greater pain bothersomeness relief compared to sham acupuncture (p = 0.14). Additional analysis showed that there was no significant difference on the sensations evoked by different treatment modalities. Conclusion These findings support VGAIT as a promising method for pain management.

Acute Exercise Increases Pain Threshold And Subjective Psychoactive Mood State

Prescription pain medication can be addictive and have long-term health consequences. Alternative pain-relieving strategies are becoming increasingly sought after. Exercise is known to have a pain-relieving effect which is thought to be mediated through the dopaminergic system. PURPOSE: To examine the relationships between minimum pain threshold (MPT), exercise blood lactate (EBL), and the self-reported psychoactive effects of exercise based on questions from the Morphine-Benzedrine Group, Morphine and Excitement subscales of the Addiction Research Center Inventory (ARCI) following acute exercise in college aged students. METHODS: Twelve college aged students (age = 20.9 ± 0.5yr) underwent 5 minutes of light leg cycling as a warmup. Following the warmup, they cycled for 20 minutes at 8 METS with an additional 5-minute cooldown. Measurements were taken prior to exercise and just before the cool down. EBL was collected as a measure of relative exercise intensity. The MPT was measured using a Wagner “Pain Test” algometer on the extensor carpi radialis. Results were assessed using a Student’s T-Test. RESULTS: Following exercise the MPT was increased by 62.1% ± 2.8 (P<0.001). Women had a greater increase in MPT (25.7 ± 9.1%) relative to men (15.8 ± 9.4%; P<0.05). EBL increased from an average of 1.8 ± 0.6 mmol/L at baseline to 4.1 ± 0.7 mmol/L following exercise (P<0.01). There was a positive linear correlation between MPT and EBL (r2=0.59; P<0.05). Indicating greater EBL levels were related to increased MPT. Positive responses from the ARCI subscale increased by 27 ± 3.3% following exercise (P<0.05). There was no effect of sex nor EBL on positive responses on the ARCI. CONCLUSIONS: These data suggest moderate intensity exercise can increase MPT and to a greater extent in women. Further, MPT correlated with increased EBL indicating that greater relative exercise intensity may modulate a greater increase MPT. Moderate intensity exercise increased positive responses on the ARCI providing evidence that the dopaminergic system may drive changes to MPT. However, positive responses did not correlate to EBL which may suggest another variable may augment pain reduction with increased exercise intensity.

Downregulation of microRNA‑29c reduces pain after child delivery by activating the oxytocin‑GABA pathway.

A significant decrease in the expression of spinal microRNA-29c (miR-29c), which is responsible for the regulation of oxytocin receptor (OXTR) expression, was observed in nerve injury pain during childbirth. The present study investigates whether spinal miR-29c could be a potential target for the treatment of pain, via the oxytocin (OT)-γ-aminobutyric acid (GABA) pathway. A spared nerve injury (SNI) rat model was established to induce neuropathic pain, simulating hyperalgesia. Spinal neurons were treated with OT to mimic the hormonal changes in the central nervous system after delivery. A change in the neuronal miniature inhibitory postsynaptic currents (mIPSCs) was observed in neurons, following the silencing of miR-29c or OT treatment with or without OXTR antagonist. The Von-Frey apparatus was used to measure the animal behaviors. Molecular biological experiments and electrophysical recordings in vivo and in vitro were performed to reveal the potential analgesic mechanisms. miR-29c was significantly downregulated (more than 8-fold) in the spinal dorsal horn of delivery+SNI rats compared with the SNI rats. The silencing of miR-29c resulted in increased pain threshold in SNI rats. Bioinformatics analysis indicated that OXTR was a potential target gene of miR-29c. The delivery+SNI rats presented with higher levels of OT in the cerebrospinal fluid compared with SNI rats, which indicated that the OT signaling pathway may participate in pain relief response. The increased expression of OXTR and GABA in delivery+SNI rats were observed in the miR-29c-silenced SNI rat model, suggesting that the silencing of miR-29c can mediate pain relief by enhancing the OT-GABA pathway. In addition, an electrophysiology assay was performed to assess the mIPSCs in neurons. The silencing of miR-29c in neurons increased the frequency and amplitude of mIPSCs but there was no influence on the decay time, which suggested that the spinal inhibitory neurons became more active, subsequently reducing the feeling of pain. The inhibition of OXTR reversed the enhanced inhibitory postsynaptic currents, indicating a crucial role for OXTR in the miR-29c-associated pain regulation. Taken together, the results of the present study suggested that spinal oxytocinergic inhibitory control plays an important role in pain relief in the neuropathic pain rat model undergoing vaginal delivery. Silencing spinal miR-29c may be a potential target for pain relief through the OT-GABA pathway.

Sex dependent alterations of resveratrol on social behaviors and nociceptive reactivity in VPA-induced autistic-like model in rats

IntroductionThe present study was designed to clarify the effects of resveratrol (RSV) on social behavioral alterations and nociceptive reactivity in valproic acid (VPA)-induced autistic-like model in female and male rats. MethodsPregnant Wistar rats were randomly divided in five groups. Animals received saline, DMSO, VPA, RSV and RSV + VPA. VPA was administered (600 mg/kg, i. p.) on embryonic day 12.5 (E12.5) and pretreatment by resveratrol (3.6 mg/kg, s. c.) was applied on E6.5 until E18.5. All offspring were weaned on postnatal day 21 and the experiments were done in male and female rats on day 60. Social interaction, hot plate and tail flick tests were set out to assess social deficits and pain threshold, respectively. Sociability index (SI), Social novelty index (SNI) and latency time were calculated as the standard indices of social behaviors and pain threshold, respectively. ResultsThe results indicated that systemic intraperitoneal administration of VPA (600 mg/kg) significantly decreased SI and SNI in social interaction test (SIT) especially in male rats, indicating the social impairments caused by VPA. RSV (3.6 mg/kg, s. c.) reversed VPA-induced social deficits in male rats, but not in female group. VPA administration resulted in significant increase in latency time in the hot plate and tail flick tests in male rats, whereas it had no such dramatic effect in females. RSV administration in combination with VPA had no significant effect on latency time compared to the valproic acid group in male rats. It is important to note that RSV by itself had no significant effect on SI, SNI and latency time in female and male rats. ConclusionIt can be concluded that valproic acid produces autistic-like behaviors and increases pain threshold in male rats which may be ameliorated at least in part by resveratrol administration. Further studies are needed to elucidate the molecular mechanisms involved in valproic acid and resveratrol-induced effects.

The effect of vibration therapy on neck myofascial trigger points: A randomized controlled pilot study

BackgroundThe purpose of this study was to evaluate the effect of low-frequency self-administered vibration therapy into myofascial trigger points in the upper trapezius and levator scapulae on patients with chronic non-specific neck pain. MethodsTwenty-eight patients with chronic non-specific neck pain were randomly assigned into a vibration group, receiving 10 self-applied sessions of vibration therapy in the upper trapezius and levator scapulae trigger points; or a control group, receiving no intervention. Self-reported neck pain and disability (Neck Disability Index) and pressure pain threshold were assessed at baseline and after the first, fifth and 10th treatment sessions. FindingsSignificant differences were found in the vibration group when compared to the control group after the treatment period: the vibration group reached lower Neck Disability Index scores (F = 4.74, P = .033, η2 = 0.07) and greater pressure pain threshold values (F = 7.56, P = .01, η2 = 0.10) than the control group. The vibration group reported a significant reduction in Neck Disability Index scores (χ2 = 19,35, P = .00, Kendall's W = 0.28) and an increase in pressure pain threshold (χ2 = 87,10, P = .00, Kendall's W = 0.73) between the assessment times over the course of the treatment. The mean increase in pressure pain threshold in the vibration group after the 10 sessions was 8.54 N/cm2, while the mean reduction in Neck Disability Index scores was 4.53 points. InterpretationVibration therapy may be an effective intervention for reducing self-reported neck pain and disability and pressure pain sensitivity in patients with chronic non-specific neck pain. This tool could be recommended for people with non-specific neck pain.

Effect of electroacupuncture on the morphological changes of the spinal dorsal horn and the expression of p38 mitogen-activated protein kinase in the injured spinal cord of rats with neuropathic pain

To investigate the effect of electroacupuncture stimulation at "Zusanli"(ST36) and "Kunlun"(BL60) on the morphological changes of the spinal dorsal horn and the expression of p38 mitogen-activated protein kinase (p38MAPK) in the injured spinal cord of rats with neuropathic pain. Male Sprague-Dawley rats were randomly divided into sham model group, model group, electroacupuncture group, and medication group, with 10 rats in each group. Spinal nerve ligation of the L5 lumbar vertebra was performed to establish a rat model of neuropathic pain. The rats in the electroacupuncture group were given electroacupuncture at ST36 and BL60 of the operation side with dilatational wave at a frequency of 2 Hz/100 Hz and an intensity of 1.5 mA once a day, 30 minutes each time, and those in the medication group were given intraperitoneal injection of 100 mg/mL Gabapentin solution (100 mg/kg) once a day; the one-week intervention was started at one week after surgery. Mechanical withdraw threshold (MWT) and thermal withdrawal latency (TWL) were observed and recorded before modeling and on days 1,3,5,7,10,12 and 14 after modeling, and the motor function of the affected hindlimb was scored. Methenamine silver stain was used to observe the morphological changes of the spinal dorsal horn, and Western blot was used to measure the relative protein expression of p38MAPK and phospho-p38MAPK(p-p38MAPK) in L4-L6 spinal segments. Compared with the sham model group, the model group had significant reductions in MWT and TWL at each time point (P<0.001) and a significant increase in motor function score (P<0.001); compared with the model group, the electroacupuncture group and the medication group had significant increases in MWT and TWL and a significant reduction in motor function score after treatment (P<0.05). The model group had obvious neuronal fibrillary tangles, particle vacuolar degeneration, and vacuoles containing argyrophilic grains in the cytoplasm of neural cells under a light microscope, while there were fewer neuronal fibrillary tangles in the electroacupuncture group and reduced vacuolar degeneration in the medication group. Compared with the sham model group, the model group had significant increases in the protein expression of p-p38MAPK in the spinal dorsal horn (P<0.001), and compared with the model group, the electroacupuncture group and the medication group had significant reductions in the protein expression of p-p38MAPK in the spinal dorsal horn(P<0.05). Electroacupuncture stimulation at ST36 and BL60 can increase pain threshold, improve the motor function of the affected hindlimb, and improve the necrosis of neurofibrils in the spinal dorsal horn in rats with neuropathic pain, possibly by regulating the expression of p-p38MAPK in the spinal dorsal horn.

The Association of Psychosocial Factors and Exercise-Induced Hypoalgesia in Healthy People and People With Musculoskeletal Pain: A Systematic Review.

Exercise, a cornerstone in current treatments for people with musculoskeletal pain, elicits a phenomenon called exercise-induced hypoalgesia (EIH), which may result in reduced pain intensity and/or increased pain thresholds. However, EIH can be impaired in patients with musculoskeletal pain, and psychosocial factors may play a mediating role in EIH. The aim of this study was to systematically review the scientific literature regarding the association between psychosocial factors and EIH in healthy people and people with musculoskeletal pain. An extensive search in databases including Medline Ovid, Embase, Web of Science, PsycINFO Ovid, and the Cumulative Index to Nursing and Allied Health Literature (CINAHL) EBSCOhost was carried out. Two reviewers independently carried out study selection, data extraction, and critical appraisal. Included studies analyzed the association or effect of psychosocial factors on EIH in adults with or without musculoskeletal pain. Nine cross-sectional studies were included, 6 involving healthy people and 4 involving people with musculoskeletal pain; 1 study included both. Overall risk of bias was high. Different types of exercise bouts, psychosocial factors, and/or outcome measures were used across studies. In healthy people and people with musculoskeletal pain, most studies did not find an association between psychosocial factors and EIH. However, 1 study involving musculoskeletal pain and 2 studies with healthy people did find a significant association. Due to poor quality and heterogeneity between studies, no conclusions can be drawn regarding whether psychosocial factors are associated with EIH or not. This review includes recommendations and directions for further research to investigate the role of psychosocial factors on EIH.

Swearing as a Response to Pain: Assessing Hypoalgesic Effects of Novel "Swear" Words.

Previous research showing that swearing alleviates pain is extended by addressing emotion arousal and distraction as possible mechanisms. We assessed the effects of a conventional swear word (“fuck”) and two new “swear” words identified as both emotion-arousing and distracting: “fouch” and “twizpipe.” A mixed sex group of participants (N = 92) completed a repeated measures experimental design augmented by mediation analysis. The independent variable was repeating one of four different words: “fuck” vs. “fouch” vs. “twizpipe” vs. a neutral word. The dependent variables were emotion rating, humor rating, distraction rating, cold pressor pain threshold, cold pressor pain tolerance, pain perception score, and change from resting heart rate. Mediation analyses were conducted for emotion, humor, and distraction ratings. For conventional swearing (“fuck”), confirmatory analyses found a 32% increase in pain threshold and a 33% increase in pain tolerance, accompanied by increased ratings for emotion, humor, and distraction, relative to the neutral word condition. The new “swear” words, “fouch” and “twizpipe,” were rated as more emotional and humorous than the neutral word but did not affect pain threshold or tolerance. Changes in heart rate and pain perception were absent. Our data replicate previous findings that repeating a swear word at a steady pace and volume benefits pain tolerance, extending this finding to pain threshold. Mediation analyses did not identify a pathway via which such effects manifest. Distraction appears to be of little importance but emotion arousal is worthy of future study.