Assessment Of Pain Sensitivity Research Articles

Pain Sensitivity Questionnaire: Cross-cultural adaptation and validation of the Greek version.

The Pain Sensitivity Questionnaire (PSQ) was developed to assess general pain sensitivity. This study aimed to validate the Greek version of PSQ. The questionnaire was translated into Greek (PSQ-GR) and piloted in a small sample of patients with chronic pain (n=35). A total of 146 chronic pain patients and healthy volunteers completed the PSQ-GR, the Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS) and Central Sensitization Inventory (CSI). To evaluate the test-retest reliability, 36 volunteers completed the PSQ-GR twice over 7±2days. Internal consistency was excellent (Cronbach's alpha 0.90-0.96) for PSQ-total, PSQ-minor, and PSQ-moderate. The Intraclass Correlation Coefficient was estimated at 0.90-0.96 for PSQ-total, PSQ-minor and PSQ-moderate and the SEM was 0.59-0.90 for PSQ-total, PSQ-minor and PSQ-moderate approximately. The smallest detectable change was 0.48 for PSQ-total, 0.47 for PSQ-minor and 0.44 for PSQ-moderate. Positive and significant correlations were observed between PSQ-GR and HADS (r=0.38, p<0.01), PCS (r=0.41, p<0.01) and CSI (r=0.30, p<0.01). Statistically significant differences in PSQ-GR scores were identified between the healthy volunteers and the chronic pain patients. The PSQ-GR is a reliable and valid tool that can assess pain sensitivity in healthy individuals and chronic musculoskeletal pain patients.

The effect and mechanism of low-dose esketamine in neuropathic pain-related depression-like behavior in rats

BackgroundClinical evidence suggests that Esketamine (ESK) is an effective treatment for depression. However, the effects of Esketamine in treating depression-like behavior induced by neuropathic pain is unclear. The underlying molecular mechanisms require further investigation to provide new therapeutic targets for the treatment of clinical neuropathic pain-related depression. MethodsA neuropathic pain-related depression model was established in rats with spared nerve injury (SNI). Male Sprague-Dawley rats were randomly divided into four groups: Sham Group, SNI group, SNI + Normal Saline (NS) Group and SNI + ESK5mg/kg Group. Mechanical pain thresholds were measured to assess pain sensitivity in SNI rats. On the 14th day after surgery a forced swim test and sucrose preference test were used to evaluate the depressive-like behavior of rats in each group. Further, a proteomic analysis was used to quantify differentially expressed proteins. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed to explore the main protein targets of SNI in the medial prefrontal cortex. The expression of proteins was detected by Western blotting. ResultsA neuropathic pain-related depression model was established. Compared with the Sham group, the mechanical pain threshold was decreased significantly (13.2 ± 1.0 vs. 0.7 ± 0.01 g n = 8), while immobility on the forced swim test was also decreased (93.1 ± 7.4 vs. 169.5 ± 9.6 s n = 8), and sucrose preference rate was significantly increased (98.8 ± 0.3 vs. 73.1 ± 1.4n = 7) in SNI group rats. Compared with the SNI + NS group, the mechanical pain threshold was not statistically significant, while immobility on the forced swim test was clearly decreased (161.1 ± 11.6 vs. 77.9 ± 5.0 s n = 8), and sucrose preference rate was significantly increased (53.1 ± 8.9 vs. 96.1 ± 1.4n = 7) in SNI + ESK5mg/kg group rats. To further investigate the underlying mechanism, we employed proteomics to identify proteins exhibiting more than a 1.2-fold difference (P < 0.05) in expression levels within each group for subsequent analysis. Relative to the Sham group, 88 downregulated and 104 up-regulated proteins were identified in the SNI group, while 120 and 84 proteins were up- and down-regulated in the Esketamine treatment group compared with the SNI + NS group. Compared with Sham group, the expressions of mGluR5 and Homer1a were up-regulated in the medial prefrontal cortex (mPFC) in SNI group (mGluR5:0.97 ± 0.05 vs 1.47 ± 0.15, Homer1a:1.03 ± 0.06 vs 1.46 ± 0.16n = 6), and down-regulated after intervention with Esketamine (mGluR5:1.54 ± 0.11 vs 1.06 ± 0.07, Homer1a:1.51 ± 0.13 vs 1.12 ± 0.34n = 6). ConclusionsLow-dose Esketamine appeared to relieve depression-like behavior induced by neuropathic pain. The Homer1a-mGluR5 signaling pathway might be the mechanism of antidepressant effect of Esketamine.

Moxibustion ameliorates chronic inflammatory visceral pain via spinal circRNA-miRNA-mRNA networks: a central mechanism study

This study aimed to unveil the central mechanism of moxibustion treating chronic inflammatory visceral pain (CIVP) from the angle of circRNA-miRNA-mRNA networks in the spinal cord. The rat CIVP model was established using a mixture of 5% (w/v) 2,4,6-trinitrobenzene sulfonic acid and 50% ethanol at a volume ratio of 2:1 via enema. Rats in the moxibustion group received herb-partitioned moxibustion at Tianshu (ST25, bilateral) and Qihai (CV6) points. The abdominal withdrawal reflex (AWR), mechanical withdrawal threshold (MWT), and thermal withdrawal latency (TWL) were adopted for pain behavior observation and pain sensitivity assessment. The circRNA, miRNA, and mRNA expression profiles were detected using the high-throughput sequencing technique. Relevant databases and bioinformatics analysis methods were used to screen for differentially expressed (DE) RNAs and build a circRNA-miRNA-mRNA (competing endogenous RNA) ceRNA regulatory network. The real-time quantitative PCR was employed to verify the sequencing result. CIVP rat models had a significantly higher AWR and lower TWL and MWT than normal rats. Between normal and model rats, there were 103 DE-circRNAs, 16 DE-miRNAs, and 397 DE-mRNAs in the spinal cord. Compared with the model group, the moxibustion group had a lower AWR and higher TWL and MWT; between these two groups, there were 118 DE-circRNAs, 15 DE-miRNAs, and 804 DE-mRNAs in the spinal cord. Two ceRNA networks were chosen to be verified. As a result, moxibustion’s analgesic effect on visceral pain in CIVP rats may be associated with regulating the circRNA_02767/rno-miR-483-3p/Gfap network in the spinal cord and improving central sensitization.

Revitalizing Postoperative Pain Management in Enhanced Recovery After Surgery via Inter-departmental Collaboration Toward Precision Medicine: A Narrative Review.

This narrative review explores the crucial aspects of postoperative pain management within the framework of Enhanced Recovery After Surgery (ERAS). It emphasizes the significance of effective and secure pain management, highlighting its impact on patient well-being, surgical outcomes, and hospital stays. The inadequacy of perioperative pain relief increases the risk of persistent postoperative pain, emphasizing the need to challenge the notion that pain is expected after surgery. The goals of postoperative pain management extend beyond mere relief, encompassing comfortable sleep, pain-free rest, and liberation from pain during initial recovery. Inadequate pain management can lead to complications such as heightened postoperative bleeding and an increased risk of thrombosis. The review delves into various analgesic methods, their complications, and safety measures.ERASprograms, focused on reducing complications and medical costs, emphasize the importance of judicious postoperative pain management and active rehabilitation. The review discusses complications associated with analgesic methods like opioids, epidural analgesia, and adjuvant analgesics. Collaboration within the perioperative management team is crucial for effective postoperative pain relief. Interdepartmental collaboration is essential for evaluating surgical procedures, analgesic methods, and crisis management strategies. The review concludes by integrating precision medicine into postoperative pain management, emphasizing the potential of genetic information in assessing pain sensitivity. It underscores the importance of inter-departmental collaboration and information gathering for the successful implementation of precision medicine tailored to each facility's perioperative management systems. Additionally, the impact of artificial intelligence (AI) on preoperative risk assessment and innovative monitoring techniques is discussed, paving the way for the advancement of precision medicine in postoperative pain management.

Structural alterations and pain perception at the ankle joint in patients with haemophilia.

Patients with haemophilia (PwH) suffer from chronic pain due to joint alterations induced by recurring haemorrhage. This study aimed to investigate the relationship between structural alterations and pain perception at the ankle joint in PwH. Ankle joints of 79 PwH and 57 healthy controls (Con) underwent ultrasound examination (US) and assessment of pain sensitivity via pressure pain thresholds (PPT). US discriminated between joint activity (synovitis) and joint damage (cartilage and/or bone degeneration) applying the HEAD-US protocol. Based on US-findings, five subgroups were built: PwH with activity/damage, PwH with activity/no damage, PwH with no activity/no damage, controls with activity/no damage and controls with no activity/no damage. Joint activity and joint damage were significantly increased in ankles of PwH compared to Con (p ≤.001). Subgroup analysis revealed that structural alterations negatively impact pain perception. This is particularly evident when comparing PwH with both activity/damage to PwH with no activity/no damage at the tibiotalar joint (p=.001). At the fibulotalar joint, no significant differences were observed between PwH subgroups. Further analysis showed that both joint activity and joint damage result in an increase in pain sensitivity (p ≤.001). The data suggest a relation between joint activity, joint damage and pain perception in PwH. Even minor changes due to synovitis appear to affect pain perception, with the effect not intensifying at higher levels of inflammation. In terms of joint damage, severe degeneration leads to a sensitised pain state most robustly, whereas initial changes do not seem to significantly affect pain perception.

Translation, cross-cultural adaptation, and measurement properties of the Arabic version of the pain sensitivity questionnaire.

The Pain Sensitivity Questionnaire (PSQ) is a reliable and valid self-reported tool for the assessment of pain sensitivity in clinical practice. The PSQ has been translated, validated, and cross-culturally adapted into multiple languages. However, a validated Arabic version of the PSQ is not available. Thus, this study aims to translate, validate, and cross-culturally adapt the English version of the PSQ into the Arabic language. The English version of the PSQ was translated and culturally adapted into Arabic following international guidelines. The psychometric properties of the final version of the PSQ-Arabic (PSQ-A) were tested among 119 patients with different persistent musculoskeletal (MSK) pain. The Cronbach's α for the PSQ-A-total, PSQ-A-moderate, and PSQ-C-minor were 0.81, 0.79, and 0.76, respectively. The means for the PSQ-A-total, PSQ-A-moderate, and PSQ-C-minor scores were 5.07 (±1.28), 5.64 (±2.07), and 4.50 (±0.50). The test-retest reliability measured with the interclass correlation coefficient for 68 subjects was 0.80 for the PSQ-A-total, 0.74 for the PSQ-A-moderate, and 0.77 for the PSQ-A-minor. The PSQ-A-total and the PSQ-A-minor showed positive significant correlations with pain catastrophizing scale (PCS) (r = 0.15, 0.17); P ≤ 0.05), respectively. The PSQ-A-total, PSQ-A-moderate, and PSQ-A-minor showed positive significant correlations with the Brief Pain Inventory (BPI)-pain scores (r = 0.47, 0.43, 0.45; P ≤ 0.01), respectively and with the BPI-pain interference scores (r = 0.37, 0.33, 0.34; P ≤ 0.01), respectively. This study shows that the PSQ-A is a reliable and valid tool to assess individuals with pain sensitivity in Arabic populations. Further studies are recommended to examine the concurrent validity of the PSQ-A against experimental pain sensitivity measures.

Trigeminocervical pain sensitivity during the migraine cycle depends on headache frequency

ObjectiveThis experimental study aimed to assess pain sensitivity in low-frequency episodic migraine (LFEM), high-frequency episodic migraine (HFEM), and chronic migraine (CM) patients across the different phases of the migraine cycle.MethodIn this observational, experimental study, clinical characteristics (diary and time from the last/next headache attack), and quantitative sensory testing (QST) (wind-up pain ratio (WUR) and pressure pain threshold (PPT) from the trigeminal area and PPT from the cervical spine) was performed. LFEM, HFEM, and CM were assessed in each of the 4 migraine phases (HFEM and LFEM: interictal, preictal, ictal, and postictal; CM: interictal and ictal) and compared vs. each other’s (matched for the phase) and controls.ResultsA total of 56 controls, 105 LFEM, 74 HFEM, and 32 CM were included. No differences in QST parameters were observed between LFEM, HFEM, and CM in any of the phases.During the interictal phase and when comparing with controls the following were found: 1) LFEM had lower trigeminal PPT (p = 0.001) and 2) lower cervical PPT (p = 0.001). No differences were observed between HFEM or CM and healthy controls. During the ictal phase and when comparing with controls the following were found: HFEM and CM had 1) lower trigeminal PPTs (HFEM p = 0.001; CM = p < 0.001), 2) lower cervical PPT s (HFEM p = 0.007; CM p < 0.001), and 3) higher trigeminal WUR (HFEM p = 0.001, CM p = 0.006). No differences were observed between LFEM and healthy controls. During the preictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.007), 2) HFEM had lower trigeminal (p = 0.013) and 3) HFEM had lower cervical (p = .006) PPTs. During the postictal phase and when comparing with controls the following were found: 1) LFEM had lower cervical PPT (p = 0.003), 2) HFEM had lower trigeminal PPT (p = 0.005), and 3) and HFEM had lower cervical (p = 0.007) PPTs.ConclusionThis study suggested that HFEM patients have a sensory profile matching CM better than LFEM. When assessing pain sensitivity in migraine populations, the phase with respects to headache attacks is of utmost importance and can explain the inconsistency in pain sensitivity data reported in the literature.

The effective on intradermal acupuncture based on changes in biological specificity of acupoints for major depressive disorder: study protocol of a prospective, multicenter, randomized, controlled trial

BackgroundAntidepressants still have some side effects in treating major depressive disorder (MDD), and acupuncture therapy is a complementary therapy of research interest for MDD. Acupoints are sensitive sites for disease response and stimulation points for acupuncture treatment. Prior studies suggest that the biological specificity of acupoints is altered in physiological and pathological situations. Therefore, we hypothesize that the biological specificity of acupoints is associated with the diagnosis of MDD and that stimulating acupoints with significant biological specificity can achieve a better therapeutic effect than clinical common acupoints. This study aims to investigate the efficacy and safety of intradermal acupuncture (IA) treatment for MDD based on changes in the biological specificity of acupoints.MethodsThe first part of the study will enroll 30 MDD patients and 30 healthy control (HC) participants to assess pain sensitivity and thermal specificity of MDD-related acupoints using a pressure pain threshold gauge (PTG) and infrared thermography (IRT). The potentially superior acupoints for treating MDD will be selected based on the results of PTG and IRT tests and referred to as pressure pain threshold strong response acupoints (PSA) and temperature strong response acupoints (TSA).The second part of the study will enroll 120 eligible MDD patients randomly assigned to waiting list (WL) group, clinical common acupoint (CCA) group, TSA group, and PSA group in a 1:1:1:1 ratio. The change in the Patient Health Questionnaire-9 Items (PHQ-9), the MOS item short-form health survey (SF-36), pressure pain threshold, temperature of acupoints, and adverse effects will be observed. The outcomes of PHQ-9 and SF-36 measures will be assessed before intervention, at 3 and 6 weeks after intervention, and at a 4-week follow-up. The biological specificity of acupoint measures will be assessed before intervention and at 6 weeks after intervention. All adverse effects will be assessed.DiscussionThis study will evaluate the therapeutic effect and safety of IA for MDD based on changes in the biological specificity of acupoints. It will investigate whether there is a correlation between the biological specificity of MDD-related acupoints and the diagnosis of MDD and whether stimulating strong response acupoints is superior to clinical common acupoints in the treatment of MDD. The study’s results may provide insights into the biological mechanisms of acupuncture and its potential as a complementary therapy for MDD.Clinical Trial RegistrationClinicalTrials.gov, identifier: NCT05524519.

Preoperative pain sensitivity predicts postoperative pain severity and analgesics requirement in lumbar fusion surgery – a prospective observational study

BACKGROUND CONTENTThe goal of postoperative pain management is to facilitate the patient's return to normal activity and decrease the detrimental effects of acute postsurgical pain. In order to provide more tailored and successful pain treatment, it is necessary to identify individuals who are at a high risk of experiencing severe postoperative pain. The most precise way to assess pain sensitivity is by determining the pressure pain threshold and heat pain threshold by objective methods using a digital algometer and neurotouch respectively. PURPOSEThe primary aim of the study is to assess the preoperative pain threshold and its influence on postoperative pain severity and analgesics requirements in patients undergoing lumbar fusion surgeries. STUDY DESIGNProspective, observational study. PATIENT SAMPLESixty patients requiring a single-level lumbar fusion surgery. OUTCOME MEASURESPostoperative pain intensity and the amount of postoperative analgesics consumption. METHODSIn our patients, preoperative pain sensitivity was assessed by pressure pain threshold measurements with the help of a digital algometer, and heat pain threshold using a neurotouch instrument. In addition, pain sensitivity questionnaires (PSQ) were used in all our patients to determine pain sensitivity. Preoperative psychosocial and functional assessments were performed by Hospital anxiety-depression scores (HADS), and Oswestry disability index (ODI) respectively. Preoperative visual analog scale (VAS) score was determined at three instances of needle prick (phlebotomy, glucometer blood sugar, and intradermal antibiotic test dose) and during the range of movements of the lumbar spine region. Postoperative VAS score and postoperative breakthrough analgesic requirements were recorded in all of these patients from day 0 to day 3. RESULTSThe average age of the patients was 51.11±13.467 years and 70% were females. Females had lower mean algometry values (72.14±7.56) compared to males (77.34±6.33). Patients with higher HADS (p<.0016), higher PSQ (p<.001), higher ODI scores(p<.001), and female gender significantly correlated with a lower algometer average indicating high pain sensitivity. Patients with lower preoperative VAS scores and with higher neurotouch scores showed lower postoperative VAS scores at different time periods. Preoperative VAS scores, algometer average scores, neurotouch scores, and HADS scores were considered as independent variables (predictors) for postoperative VAS at 6 hours period. By the multivariate analysis, factors like preoperative VAS scores, algometer average scores, and HADS scores were statistically significant (p<.05). There was a significant correlation between algometer average scores (p<.001) with the breakthrough analgesics. CONCLUSIONPreoperative assessment of pain sensitivity can predict postoperative analgesic requirements and aid in recovery. Patients with a lower pain threshold should be counseled preoperatively and also receive a better titration of analgesics perioperatively.

Low-Intensity Blood Flow Restriction Exercises Modulate Pain Sensitivity in Healthy Adults: A Systematic Review

Low-intensity exercise with blood flow restriction (LIE-BFR) has been proposed as an effective intervention to induce hypoalgesia in both healthy individuals and patients with knee pain. Nevertheless, there is no systematic review reporting the effect of this method on pain threshold. We aimed to evaluate the following: (i) the effect of LIE-BFR on pain threshold compared to other interventions in patients or healthy individuals; and (ii) how different types of applications may influence hypoalgesic response. We included randomized controlled trials assessing the effectiveness of LIE-BFR alone or as an additive intervention compared with controls or other interventions. Pain threshold was the outcome measure. Methodological quality was assessed using the PEDro score. Six studies with 189 healthy adults were included. Five studies were rated with 'moderate' and 'high' methodological quality. Due to substantial clinical heterogeneity, quantitative synthesis could not be performed. All studies used pressure pain thresholds (PPTs) to assess pain sensitivity. LIE-BFR resulted in significant increases in PPTs compared to conventional exercise at local and remote sites 5 min post-intervention. Higher-pressure BFR results in greater exercise-induced hypoalgesia compared to lower pressure, while exercise to failure produces a similar reduction in pain sensitivity with or without BFR. Based on our findings, LIE-BFR can be an effective intervention to increase pain threshold; however, the effect depends on the exercise methodology. Further research is necessary to investigate the effectiveness of this method in reducing pain sensitivity in patients with pain symptomatology.

War experiences and relationship problems predict pain sensitivity cross-sectionally among patients with chronic primary pain

Background: Most patients suffering from chronic pain are more susceptible to pain and pressure due to higher pain sensitivity. Since psychosocial factors play a central role in developing and maintaining chronic pain, investigating associations between pain sensitivity and psychosocial stressors promises to advance the biopsychosocial understanding of chronic pain. Objectives: We aimed to replicate Studer et al.'s (2016) findings about associations of psychosocial stressors with pain sensitivity in a new sample of patients with chronic primary pain (ICD-11, MG30.0). Methods: A pain provocation test was used on both middle fingers and earlobes to assess pain sensitivity among 460 inpatients with chronic primary pain. Potentially life-threatening accidents, war experiences, relationship problems, certified inability to work, and adverse childhood experiences were assessed as potential psychosocial stressors. Structural equation modeling was used to investigate associations between psychosocial stressors and pain sensitivity. Results: We partially replicated Studer et al.'s findings. Similar to the original study, patients with chronic primary pain showed enhanced pain sensitivity values. Within the investigated group, war experiences (β = 0.160, p < .001) and relationship problems (β = 0.096, p = .014) were associated with higher pain sensitivity. In addition, the control variables of age, sex, and pain intensity also showed a predictive value for higher pain sensitivity. Unlike Studer et al., we could not identify a certified inability to work as a predictor of higher pain sensitivity. Conclusions: This study showed that beyond age, sex, and pain intensity, the psychosocial stressors of war experiences and relationship problems were associated with higher pain sensitivity.

Contributions of SARM1 to neuropathic pain vary across nerve injury models

The purpose of this study is to determine if Sarm1 is required for the development of nerve injury induced neuropathic pain. Neuropathic pain after nerve injury often manifests as mechanical allodynia and thermal hyperalgesia. Wallerian degeneration has been reported to play a role in the development of nerve injury induced neuropathic pain. In addition, sterile alpha and TIR motif containing 1 (Sarm1) is a protein required for Wallerian degeneration and has been implicated in several non-axotomy neuropathic pain models. It is thus of our interest to determine the requirement of Sarm1 for the development of nerve injury induced neuropathic pain. Either the spared nerve injury (SNI), L4 Spinal Nerve Ligation (SNL), or chronic constriction injury (CCI) nerve injury model was performed on Sarm1KO mice and their littermate WT controls. Behavioral assays of evoked mechanical (von Frey, dynamic brush) and thermal (Hargreaves) sensitivity were performed at multiple time points before and after surgery to assess pain sensitivity. Alternatively, mice were videorecorded after injury and their spontaneous pain-related behaviors scored. Results Sarm1KO mice did not exhibit deficits in development of punctate or dynamic brush mechanical allodynia after CCI. Interestingly, however, Sarm1KO did exhibit a delay in development of heat hyperalgesia after CCI compared to WT controls. By contrast, Sarm1KO mice did not show deficits in development of either mechanical allodynia or thermal hyperalgesia after SNI and L4 SNL surgeries. However, preliminary results suggest a trend towards reduced spontaneous pain behaviors after SNI in SARM1 KO, compared to WT controls. Our data suggest that Sarm1 is required for the normal development of heat hyperalgesia but not mechanical allodynia after CCI. In summary, the role of Sarm1 in nerve injury induced neuropathic pain is both model and modality dependent. Grant support from Neurosurgery Pain Research Institute at Johns Hopkins Dr. Miriam and Sheldon Adelson Medical Research Foundation. The purpose of this study is to determine if Sarm1 is required for the development of nerve injury induced neuropathic pain. Neuropathic pain after nerve injury often manifests as mechanical allodynia and thermal hyperalgesia. Wallerian degeneration has been reported to play a role in the development of nerve injury induced neuropathic pain. In addition, sterile alpha and TIR motif containing 1 (Sarm1) is a protein required for Wallerian degeneration and has been implicated in several non-axotomy neuropathic pain models. It is thus of our interest to determine the requirement of Sarm1 for the development of nerve injury induced neuropathic pain. Either the spared nerve injury (SNI), L4 Spinal Nerve Ligation (SNL), or chronic constriction injury (CCI) nerve injury model was performed on Sarm1KO mice and their littermate WT controls. Behavioral assays of evoked mechanical (von Frey, dynamic brush) and thermal (Hargreaves) sensitivity were performed at multiple time points before and after surgery to assess pain sensitivity. Alternatively, mice were videorecorded after injury and their spontaneous pain-related behaviors scored. Results Sarm1KO mice did not exhibit deficits in development of punctate or dynamic brush mechanical allodynia after CCI. Interestingly, however, Sarm1KO did exhibit a delay in development of heat hyperalgesia after CCI compared to WT controls. By contrast, Sarm1KO mice did not show deficits in development of either mechanical allodynia or thermal hyperalgesia after SNI and L4 SNL surgeries. However, preliminary results suggest a trend towards reduced spontaneous pain behaviors after SNI in SARM1 KO, compared to WT controls. Our data suggest that Sarm1 is required for the normal development of heat hyperalgesia but not mechanical allodynia after CCI. In summary, the role of Sarm1 in nerve injury induced neuropathic pain is both model and modality dependent. Grant support from Neurosurgery Pain Research Institute at Johns Hopkins Dr. Miriam and Sheldon Adelson Medical Research Foundation.

Vagus nerve stimulation modulates hippocampal inflammation caused by continuous stress in rats

BackgroundPrevious studies have shown that vagus nerve stimulation (VNS) can attenuate inflammatory responses in peripheral tissues and also improve some neurological disorders and cognitive function in the brain. However, it is not clear how VNS is involved in neuropathological processes in brain tissues. Here, we investigated the regulatory effects of VNS on the production of proinflammatory cytokines in the hippocampus of an animal model of continuous stress (CS).MethodsCS was induced by placing rats in cages immersed with water, and acute or chronic electrical stimulation was applied to the cervical vagus nerve of CS animals. Protein levels in the gastric and hippocampal tissues were measured by western blotting and protein signals analyzed by immunofluorescence staining. von Frey test and forced swimming test were performed to assess pain sensitivity and depressive-like behavior in rats, respectively.ResultsLevels of TNF-α, IL-1β, and IL-6 in the gastric and hippocampal tissues were significantly increased in CS animals compared to the untreated control and downregulated by acute VNS (aVNS). Iba-1-labeled microglial cells in the hippocampus of CS animals revealed morphological features of activated inflammatory cells and then changed to a normal shape by VNS. VNS elevated hippocampal expression of α7 nicotinic acetylcholine receptors (α7 nAChR) in CS animals, and pharmacological blockade of α7 nAChR increased the production of TNF-α, IL-1β, and IL-6, thus suppressing cholinergic anti-inflammatory activity that was mediated by VNS. Chronic VNS (cVNS) down-regulated the hippocampal production of active form of caspase 3 and 5-HT1A receptors and also decreased levels of TNF-α, IL-1β, and IL-6 in the gastric and hippocampal tissues of CS animals. Pain sensitivity and depressive-like behavior, which were increased by CS, were improved by cVNS.ConclusionsOur data suggest that VNS may be involved in modulating pathophysiological processes caused by CS in the brain.

Coadministration of Curcumin and Hydromorphone Hydrochloride Alleviates Postoperative Pain in Rats.

This study aimed to explore the effect of curcumin and hydromorphone hydrochloride (HH) cotreatment on postoperative pain in rats. An incision + formaldehyde-induced pain rat model was established. Rats were treated with vehicle, curcumin, HH, or curcumin + HH. Paw mechanical withdrawal threshold and thermal withdrawal latency were measured at 1 d before surgery as well as 1 , 2 h, 1 , 3 , and 7 d after surgery to assess pain sensitivity. The L4-6 region of the spinal cord was collected from each rat at 2 h, 1 , 3 , and 7 d after surgery. Western blot analysis and immunohistochemical staining were carried out to detect the protein expression of pain-related genes. Quantitative real-time PCR and enzyme-linked immunosorbent assay were conducted to measure the expression and production of proinflammatory mediators. Compared with other groups, Curcumin + HH significantly reduced pain sensitivity in the model rats. Mechanistically, curcumin + HH suppressed protein expression of stromal cell-derived factor-1 (SDF-1), CXC chemokine receptor 4 (CXCR4), p-Akt, and c-fos while enhancing protein expression of nerve growth factor (NGF) in the dorsal root ganglia (DRG) of model rats. Curcumin + HH inhibited the expression and production of interleukin 1β (IL-1β), cyclooxygenase-2 (COX-2), tumor necrosis factor α (TNF-α), and p65 nuclear factor kappa B (NF-κB) in the DRG. Coadministration of curcumin and HH alleviates incision + formaldehyde-induced pain in rats, possibly by suppressing the SDF-1/CXCR4 pathway and the production of proinflammatory mediators. Our results provide curcumin and HH cotreatment as a promising therapeutic strategy in the management of postoperative pain.

Validation and Cross-Cultural Adaptation of the Spanish Version of the Pain Sensitivity Questionnaire (PSQ-S).

Experimental pain testing requires specific equipment and may be uncomfortable for patients. The Pain Sensitivity Questionnaire (PSQ) was developed to assess pain sensitivity, based on the pain intensity ratings (range: 0–10) of painful situations that occur in daily life. The main objective of this study was to carry out a cross-cultural adaptation and validation of the Spanish version of the PSQ (PSQ-S). A total of 354 subjects (296 healthy and 58 chronic pain patients) filled in the PSQ-S. A subgroup of 116 subjects performed experimental pain testing, including two modalities (cold and pressure), with different measures: pain intensity rating, pressure pain threshold, and tolerance. The validation results showed two factors: PSQ-S-moderate and PSQ-S-minor and, for the total scale and the two factors, an excellent internal consistency (Cronbach’s alpha coefficient > 0.9) and a substantial reliability (Intraclass Correlation Coefficient > 0.8). We obtained strong correlations with all the experimental pain rating parameters, catastrophizing, and depression variables, as well as moderate correlations with anxiety, central sensibilization, and impact on the quality of life. Chronic pain patients received elevated PSQ-S scores compared to healthy controls, and three cut-off values (PSQ-S-total = 7.00, PSQ-S-moderate = 7.57, and PSQ-S-minor = 6.29) based on ROC curve analyses were shown to be able to discriminate between healthy adults and adults with chronic pain. Therefore, PSQ-S may be a simple alternative to experimental pain procedures for clinical and experimental pain research.

Validation of the Turkish version of the Pain Sensitivity Questionnaire in patients with chronic pain

ObjectiveThe Pain Sensitivity Questionnaire (PSQ) is a clinically beneficial instrument that has been proven to be correlated with various experimental pain sensitivity assessments in healthy people and in patients with chronic pain. In this study, we aimed to translate the PSQ into Turkish (PSQ-T) and validate it for the measurement of pain sensitivity among Turkish people.MethodsSeventy-three patients with chronic back pain who were planning to undergo an interventional procedure completed the Brief Pain Inventory-Short Form (BPI-SF), Beck Depression Inventory (BDI), Beck Anxiety Inventory, Pain Catastrophizing Scale, and PSQ prior to their procedure. Subcutaneous infiltration of lidocaine was used as a standardized experimental pain stimulus. Pain was evaluated using a visual analog scale (VAS 1: infiltration in the hand, and VAS 2: infiltration in the procedure area)ResultsScores on the PSQ-T were significantly correlated with those on the BPI-SF. A significant positive relationship was observed between VAS 1 and VAS 2 values and the PSQ-T score, BPI pain score, and BPI interference score.ConclusionsThe PSQ-T can be used as a valid and reliable tool for the assessment of pain sensitivity in the Turkish population.

Bedside clinical tests to assess sensitization in office workers with chronic neck pain

Objective This study aimed to assess pain sensitization in individual office workers with chronic neck pain through simple bedside quantitative sensory tests (QST) and to associate the findings with pain intensity and pain catastrophizing. Methods One hundred-and-four office workers with chronic neck pain were assessed using pressure pain threshold (PPT) considering pain sensitive if PPTs were lower than 155 kPa in the upper trapezius and 245 kPa in the tibialis anterior. Pain sensitive to temporal summation of pain (TSP) was considered if there was a difference of two points in the visual analogue scale (VAS) comparing the first and last stimulus. Pain sensitive was considered to conditioned pain modulation (CPM) if the CPM-effect was less than −7.5%. Pain intensity and catastrophizing were measured using VAS and with the Pain Catastrophizing Scale. Results There was at least one pain sensitive QST finding in 66 office workers (63.5%). TSP findings were the most common (48.1%), followed by PPT’s (31.7%) and CPM (20.2%). Based on the QST findings, office workers were divided based on the number of individual QST findings, and higher pain intensity and pain catastrophizing scores were found in office workers with one (N = 38, P < 0.05) or two (N = 28, P < 0.05) compared with office workers with no QST findings (N = 38). Conclusion This study demonstrated that most office workers with chronic neck pain exhibit either widespread pressure hyperalgesia, facilitated TSP or impaired CPM, indicating pain sensitization within the central nervous system. This was associated with increased clinical pain and pain catastrophizing rumination scores.

Conditioned pain modulation and pain sensitivity in functional somatic disorders: The DanFunD study.

BackgroundDisrupted pain regulation has been proposed as a component in functional somatic disorders (FSD). The objective of this study was to examine a general population sample, encompassing three delimitations of FSD while assessing pain sensitivity and conditioning pain modulation (CPM).MethodsPressure pain thresholds (PPTs) at the tibialis and trapezius muscles were recorded at baseline. During cold pressor stimulation of the hand, the tibialis PPTs were re‐assessed and the difference from baseline measures defined the CPM effect. Participants (n = 2,198, 53% females) were randomly selected from the adult Danish population. FSD was established by self‐reported symptom questionnaires.ResultsWith a few exceptions, only weak associations were seen between PPTs and CPM in cases with FSD (p > .1). A high PPT was associated with lower odds of having multi‐organ bodily distress syndrome (ORPPT trapezius: 0.66, 95% CI: 0.49–0.88, p = .005), with the symptom profile characterized by all symptoms (ORPPT trapezius: 0.72, 95% CI: 0.58–0.90, p = .003 and ORPPT tibialis: 0.75, 95% CI: 0.62–0.91, p = .004), and with multiple chemical sensitivity (ORPPT trapezius: 0.81, 95% CI: 0.67–0.97, p = .022). High CPM was associated with high odds of having irritable bowel (ORCPM relative: 1.22, 95% CI: 1.04–1.43, p = .013 and ORCPM absolute = 2.66, 95% CI: 1.07–6.45, p = .033).ConclusionHowever, only PPT measured over the trapezius muscle were still significant after correction for multiple testing for the symptom profile characterized by all symptoms. Findings from this study do not support altered pain regulation in questionnaire‐based FSD which is in contrast with the existing presumption. Further epidemiological studies in this field are needed.SignificanceDisrupted pain regulation as measured by abnormal pain thresholds has been hypothesized as a central mechanism in Functional Somatic Disorders (FSD). The hypothesis has been raised in clinical setting where patients presented subjective and objective features of hypersensitivity. The present population‐based study does not support this notion. This points to the importance of further studies into the underlying pathophysiology mechanisms of FSD.

Replication and extension of the link between the cardiovascular system and sensitivity to social pain in healthy adults

ABSTRACT Resting blood pressure (BP) and heart rate variability (HRV) are linked to physical pain. Research also shows a link between social pain and physical pain, and an inverse association between resting BP and social pain. However, little is known regarding the relationship between resting HRV and social pain. Therefore, the present study aimed to replicate the link between social pain and physical pain, and the inverse relationship between resting BP and social pain, and explore the relationship between resting HRV and social pain. One-hundred twenty three healthy adults completed 1) resting cardiovascular measurements of BP and low-frequency (LF) and high-frequency (HF) HRV powers, 2) social pain sensitivity assessment via the Brief Fear of Negative Evaluation (BFNE) and Mehrabian’s Sensitivity to Rejection (MSR) scales, and 3) physical pain sensitivity assessment via subjective pain responses during cold pressor test. The results indicated that no association was observed between social pain and physical pain, whereas resting BP was inversely associated with the MSR scores. Resting LF-HRV was inversely associated with social pain, whereas resting HF-HRV was positively associated with social pain. These findings suggest that physical pain and social pain may share biological substrates that are involved in BP regulation and pain control.

Spinal manipulation and modulation of pain sensitivity in persistent low back pain: a secondary cluster analysis of a randomized trial

BackgroundPain hypersensitivity can be assessed using Quantitative Sensory Testing (QST) and is associated with persistent low back pain. Spinal manipulation appears to modify pain hypersensitivity, and this could function as one mechanism leading to clinical improvements. In the current study, we applied a comprehensive QST battery to assess pain sensitivity in a cohort of low back pain patients before and after spinal manipulation to improve our understanding of the association between QST and clinical improvements. This study addresses two questions: Are clinical improvements following spinal manipulation in low back pain patients contingent on pain hypersensitivity, and does pain sensitivity change following spinal manipulation?MethodsWe performed a secondary analysis of data from a randomized clinical trial. One hundred and thirty-two participants with persistent LBP were treated with spinal manipulation four times over two weeks. Patient-reported outcomes and QST were assessed at baseline, after the fourth spinal manipulation session, and 14-days later. The clinical outcomes were changes in low back pain intensity and disability. Using latent profile analysis, we categorized the participants into clusters depending on their baseline QST scores. We used linear mixed models to examine the association between clusters and changes in patient-reported outcomes and QST.ResultsTwo clusters emerged: a Sensitized and a Not sensitized. The former had significantly lower regional pressure and thermal pain thresholds, remote pressure pain tolerance, and lower inhibitory conditioned pain modulation than the Not sensitized group. However, we only found between-cluster differences for regional pressure pain threshold following spinal manipulation. Thus, the clusters were not associated with patient-reported pain and disability changes or the remaining QST outcomes.ConclusionsWe report that the baseline QST profile was not associated with clinical improvements following spinal manipulation. We did observe a substantial change for regional pressure pain threshold, which suggests that any effect of spinal manipulation on pain sensitivity is most likely to be observed as changes in regional, mechanical pain threshold. However, the mechanism that invokes clinical improvement and pain sensitivity changes appear distinct. Due to methodological caveats, we advise caution when interpreting the results.Trial registrationClinical.Trial.gov identifier: NCT04086667, registered 11 September 2019 – Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04086667