Disrupted Cortical Homeostatic Plasticity Due to Prolonged Capsaicin-induced Pain.

Homeostatic plasticity (HP) regulates cortical excitability (CE) stability but is disrupted in persistent pain conditions. This study investigated how prolonged experimental pain affects HP and if pain relief modulates disrupted HP. Twenty-four healthy participants were randomised into a PainRelief or NoPainRelief group and attended four sessions; two sessions on consecutive days, separated by two weeks. Transcranial magnetic stimulation motor-evoked potentials reflecting CE and quantitative sensory testing (QST) measures were recorded. A capsaicin (pain condition) or placebo (control condition) patch was applied to the hand. HP was induced by cathodal-cathodal transcranial direct current stimulation (HP1) with CE assessment before and after. The PainRelief group had ice applied to the patch, while the NoPainRelief group waited for five minutes; subsequently another HP induction (HP2) and CE assessment were performed. After 24 h with the patch on, HP induction (HP3), QST, and CE recordings were repeated. Capsaicin reduced CE and the pain condition showed disrupted homeostatic responses at all time points (HP1: showed CE inhibition instead of facilitation; HP2 & HP3: lack of CE facilitation). Conversely, homeostatic responses were induced at all time points for the placebo condition. Capsaicin pain disrupts HP which is not restored by ice-induced pain relief. Future research may explore the prevention of HP disruption by targeting capsaicin-induced nociception but not pain perception.

Quantitative sensory testing as an assessment tool to predict the response to standard pain treatment in knee osteoarthritis: a systematic review and meta-analysis.

Emerging evidence suggest that quantitative sensory testing (QST) may predict the treatment response to pain-relieving therapies. This systematic review and meta-analysis focus on the predictive value of QST for pain management of knee osteoarthritis (OA). MEDLINE and EMBASE were systematically searched for all studies from year 2000 to 2023 on pretreatment QST and treatment of OA including surgical, pharmaceutical, and nonsurgical and nonpharmaceutical therapies. Preclinical studies and reviews were excluded. The systematic review followed the PRISMA guidelines and was pre-registered on the Open Science Framework website (link: https://osf.io/4FETK/, Identifier: DOI 10.17605/OSF.IO/4FETK). Meta-analysis were conducted to demonstrate the strength of the pre-treatment QST predictions on pain outcomes after OA treatments. Sixteen surgical (all on total knee arthroplasty [TKA], N = 1967), 5 pharmaceutical (4 on non-steroidal anti-inflammatory drugs [NSAIDs], N = 271), and 4 exercise-based therapy studies (N = 232) were identified. Pretreatment QST parameters predicted pain-relieving treatment outcomes in 81% of surgical, 100% of pharmaceutical, and 50% of exercise-based therapy studies. Meta-analyses found pretreatment QST profiles to predicted pain outcomes after TKA (random effects: 0.309, 95% confidence interval [CI]: 0.206-0.405, P < 0.001), NSAIDs (random effects: 0.323, 95% CI: 0.194-0.441, P < 0.001), and exercise-based therapies (random effects: 0.417, 95% CI: 0.138-0.635, P = 0.004). The overall risk of bias for the included studies was low to moderate. This systematic review and meta-analysis demonstrate weak-to-moderate associations between pretreatment QST and pain outcomes after standard OA pain treatments. Based on this work, it is hypothesized that a subset of specific pain sensitive patients with OA exist and that these patients do not respond adequately to standard OA pain treatments.

The association between sleep quality, preoperative risk factors for chronic postoperative pain and postoperative pain intensity 12 months after knee and hip arthroplasty.

BACKGROUND: Chronic postoperative pain following total joint replacement (TJA) is a substantial clinical problem, and poor sleep may affect predictive factors for postoperative pain, such as pain catastrophizing. However, the magnitude of these associations is currently unknown. This exploratory study investigated (1) the relationship between preoperative sleep quality, clinical pain intensity, pain catastrophizing, anxiety, and depression and (2) their associations with chronic postoperative pain following TJA. METHODS: This secondary analysis from a larger randomized controlled trial included rest pain intensity (preoperative and 12 months postoperative; visual analogue scale, VAS), preoperative Pittsburgh Sleep Quality Index (PSQI), Pain Catastrophizing Scale (PCS), Hospital Anxiety and Depression Scale (HADS) data from 74 knee and 89 hip osteoarthritis (OA) patients scheduled for TJA. Poor sleepers were identified based on preoperative PSQI scores higher than 5. RESULTS: Poor sleepers demonstrated higher preoperative VAS, pain catastrophizing, anxiety, and depression compared with good sleepers (all p < 0.003). Preoperative PSQI (ß = 0.23, p = 0.006), PCS (ß = 0.44, p < 0.005), and anxiety (ß = 0.18, p = 0.036) were independent factors for preoperative VAS. Preoperative VAS (ß = 0.32, p < 0.005), but not preoperative sleep quality (ß = -0.06, p = 0.5), was an independent factor for postoperative VAS. CONCLUSION: The OA patients reporting poor preoperative sleep quality show higher preoperative pain, pain catastrophizing, anxiety, and depression. High preoperative pain intensity, but not poor sleep quality, was associated with higher chronic postoperative pain intensity. Future studies are encouraged to explore associations between sleep and chronic postoperative pain.

Patients with symptomatic permanent atrial fibrillation show quantitative signs of pain sensitisation.

OBJECTIVE: Most patients with atrial fibrillation (AF) report symptoms, while one-third are asymptomatic. We hypothesised that sensory processing, in particular pain, differs in patients with symptomatic and asymptomatic AF. METHODS: Thirty individuals with permanent AF (15 symptomatic and 15 asymptomatic) completed the Atrial Fibrillation 6 (AF6) and short form 36 Health Survey questionnaires and underwent quantitative pain sensitisation testing using pressure algometry at the sternum (referred pain area) and the tibialis anterior muscle (generalised pain area). The primary objective was to assess differences in pressure pain thresholds (PPT), temporal summation of pain (TSP) and conditioned pain modulation (CPM) in the two groups. The secondary objective was to determine association of demographic and clinical parameters to measures of pain sensitisation. RESULTS: The symptomatic group had lower PPTs at both tibialis (p=0.004) and sternum (p=0.01), and impaired CPM (p=0.025) and facilitated TSP (p=0.008) at the tibialis but not sternum, compared with the asymptomatic group. The AF6 sum score was negatively correlated to PPT on both tibialis (r=-0.50, p=0.005) and sternum (r=-0.42, p=0.02) and positively correlated to TSP on both tibialis (r=0.57, p=0.001) and sternum (r=0.45, p=0.01), but not to CPM. The physical component summary score was positively correlated to the PPT on both tibialis (r=0.52, p=0.003) and sternum (r=0.40, p=0.03) and negatively to TSP on the tibialis (r=-0.53, p=0.003) but not sternum. CONCLUSIONS: Patients with symptomatic AF exhibit lower pain tolerance than patients with asymptomatic AF, as well as impaired pain inhibitory control and facilitated summation of pain, indicating that pain sensitisation may be of importance in symptomatic AF.Trial registration numberNCT04649437.

The Danish version for the Back Pain Attitudes Questionnaire - Translation and cross-cultural adaptation.

BACKGROUND: Beliefs and attitudes about back pain are relevant factors in relation to developing back pain. A Danish version of the Back Pain Attitudes Questionnaire (Back-PAQ) could be a way of assuring a more systematic examination of attitudes about back pain within patients with back pain, laypeople and healthcare professionals in Denmark. OBJECTIVES: The aim of this study was to develop a Danish version of the Back-PAQ and assess its psychometric properties. STUDY DESIGN: Study of diagnostic accuracy/assessment scale. METHOD: The adaptation was performed in several steps following the dual-panel method. The psychometric analyses included testing the reliability and validity. RESULTS: Thirty-seven individuals participated in the translation process, and the main findings were that the translated version was considered to reflect the original version and that it was considered relevant to address beliefs related to back pain. Five hundred and thirteen patients were included in principal component analysis and sixty were included in the test-retest analysis. The analysis on the 10-item version revealed a structure that was similar to the original questionnaire and explained 82% of the variance in the dataset. The test-retest analysis showed an ICC of 0.80 (95% CI 0.67-0.88) and SDC ranged from 0.78 to 2.35 with a mean of 1.61. CONCLUSION: The Back-PAQ was successfully translated and cross-culturally adapted into Danish. Its psychometrics properties showed that the Danish version of the questionnaire is valid and reliable for assessment of beliefs and attitudes regarding back pain, and may prove useful in both clinical settings and research in Denmark.

Investigating the expression of metabotropic glutamate receptors in trigeminal ganglion neurons and satellite glial cells: implications for craniofacial pain.

CONTEXT/OBJECTIVE: Previous studies have demonstrated that various subtypes of the metabotropic glutamate receptors (mGluRs) are expressed in the dorsal root ganglion (DRG) of the peripheral nervous system (PNS), implicating that glutamate potentially contributes to sensory transmission through these receptors. While mGluR expression has been investigated largely in the DRG, the present study focused on mGluR expression on neurons and satellite glial cells (SGCs) of the trigeminal ganglion (TG). MATERIALS AND METHODS: To address the presence of mGluRs in rat TG neurons and their corresponding SGCs, the trigeminal ganglia from six adult male Wistar rats were isolated and immunohistochemistry and immunocytochemistry were performed. The expression of mGluR1α-, mGluR2/3- and mGluR8 on TG neurons and SGCs was investigated in tissue slices and isolated cells. RESULTS: 35.1 ± 6.0% of the TG neurons were positive for mGluR1α, whereas 39.9 ± 7.7% and 55.5 ± 6.3% were positive for mGluR2/3 and mGluR8, respectively. Immunoreactive neurons expressing mGluRs were mainly medium- to large sized, with a smaller population of small-sized neurons showing immunoreactivity. The SGCs showed immunoreactivity toward mGluR1α and mGluR8, but not mGluR2/3, both in the tissue and in isolated cells. CONCLUSIONS: Findings from the present study showed that trigeminal neurons express mGluR1α, mGluR2/3 and mGluR8, while SGCs only express mGluR1α and mGluR8. This novel evidence may advance investigations on a possible role of mGluRs in relation to trigeminal pain transmission within the craniofacial region.