Maladaptive plasticity is linked to the chronification of diseases such as pain, but the transition from acute to chronic pain is not well understood mechanistically. Neuroplasticity in the central nucleus of the amygdala (CeA) has emerged as a mechanism for sensory and emotional-affective aspects of injury-induced pain, although evidence comes from studies conducted almost exclusively in acute pain conditions and agnostic to cell type specificity. Here, we report time-dependent changes in genetically distinct and projection-specific CeA neurons in neuropathic pain. Hyperexcitability of CRF projection neurons and synaptic plasticity of parabrachial (PB) input at the acute stage shifted to hyperexcitability without synaptic plasticity in non-CRF neurons at the chronic phase. Accordingly, chemogenetic inhibition of the PB→CeA pathway mitigated pain-related behaviors in acute, but not chronic, neuropathic pain. Cell-type-specific temporal changes in neuroplasticity provide neurobiological evidence for the clinical observation that chronic pain is not simply the prolonged persistence of acute pain.

OBJECTIVE: To explore modifiable psychosocial factors, sleep-related variables, indices of central pain processing and patients\' characteristics as potential prognostic factors for pain, shoulder function, and quality of life (QoL) 1 year after rotator cuff repair. DESIGN: This observational longitudinal study included 142 patients who were undergoing rotator cuff repair. All measures took place pre-rotator cuff repair (T0), and 12 weeks (T1) and 12 months (T2) after rotator cuff repair. METHODS: Mixed-effects linear regression modeled relationships between the Western Ontario Rotator Cuff Index (WORC, model A), the Subjective Shoulder Value (SSV, model B), and EuroQol\'s EQ-5D-5L for QoL (model C), and potential prognostic factors over time. Factors included psychosocial variables, sleep-related indices, and proxies of central pain processing. Patients\' age, sex, and body mass index complemented the analyses. RESULTS: At follow-up (T2), data from 124 participants were available for analysis. Five prognostic factors were identified for the 1-year outcome. Better expectations for symptom reduction (P<.0001, -1.4 mm) and an increase in Douleur Neuropathique 4 score (P = .0481, -0.9 mm) affected the evolution of WORC over time (model A). An increase in injury perception subscale consequence (P = .0035, 0.04%) influenced the SSV trajectory (model B). In addition, when sleep quality (P = .0011, -0.13%) and sleep efficiency (P = .0002, 0.005%) improved, the EQ-5D-5L slope was affected (model C). CONCLUSION: Addressing cognitions, pain mechanisms and sleep behavior prior to rotator cuff repair can identify people who are at risk of a poor outcome after surgery. J Orthop Sports Phys Ther 2024;54(8):530-540. Epub 4 July 2024. doi:10.2519/jospt.2024.12398.

Traditional Chinese Medicine (TCM), as a unique medical model in China, has been shown to be effective in the treatment of many diseases. It has been proven that TCM can increase the pain threshold, increase the level of endorphins and enkephalins in the body, and reduce the body\'s response to adverse stimuli. In recent years, TCM scholars have made valuable explorations in the field of pain treatment, using methods such as internal and external application of TCM and acupuncture to carry out research on pain treatment and have achieved more satisfactory results. TCM treats pain in a variety of ways, and with the discovery of a variety of potential bioactive substances for pain treatment. With the new progress in the research of other TCM treatment methods for pain, TCM will have greater potential in the clinical application of pain.

Objective: The aim of this study is to assess whether pain-inducing manual pressure (PIMP) leads to effects on pressure pain threshold (PPT) mediated by conditioned pain modulation (CPM) and whether these effects are influenced by the intensity and repetition of the stimulus. Additionally, the influence of psychological factors and physical activity on the response to PIMP was explored. Methods: A total of 72 pain-free students were randomly assigned to three crossover trials. Trial 1 compared the effects of PIMP with the cold pressor task and pain-inducing electrostimulation. Trial 2 compared the effects of manual pressure that elicited moderate pain, mild pain, and no pain. Trial 3 compared a single PIMP stimulation with four stimuli applied at the same site or at different sites. Results: PIMP produced a lower increase in PPT than cold pressor task and no difference with electrostimulation. Manual pressure that caused moderate pain led to a greater increase in PPT compared to mild pain and pain-free application. Repetition of PIMP stimulus, whether at the same or different sites, did not significantly increase PPT compared to a single stimulation. No association with psychological factors or physical activity was found. Conclusions: PIMP produces an increase in PPT, suggesting the involvement of CPM-related mechanisms.

Chronic pain, a complex and debilitating condition, poses a significant challenge to both patients and healthcare providers worldwide. Conventional pharmacological interventions often prove inadequate in delivering satisfactory relief while carrying the risks of addiction and adverse reactions. In recent years, electric neuromodulation emerged as a promising alternative in chronic pain management. This method entails the precise administration of electrical stimulation to specific nerves or regions within the central nervous system to regulate pain signals. Through mechanisms that include the alteration of neural activity and the release of endogenous pain-relieving substances, electric neuromodulation can effectively alleviate pain and improve patients\' quality of life. Several modalities of electric neuromodulation, with a different grade of invasiveness, provide tailored strategies to tackle various forms and origins of chronic pain. Through an exploration of the anatomical and physiological pathways of chronic pain, encompassing neurotransmitter involvement, this narrative review offers insights into electrical therapies\' mechanisms of action, clinical utility, and future perspectives in chronic pain management.

Pain in rheumatic diseases transcends the traditional nociceptive paradigm, incorporating complex interactions between nociceptive, neuropathic, and nociplastic mechanisms, as well as significant psychosocial factors. Advances in understanding chronic pain highlight the role of peripheral and central sensitization, and the emergence of nociplastic pain-a result of altered central nervous system processing. This modern perspective acknowledges the influence of mood disorders, environmental stressors, and cognitive patterns like catastrophizing, revealing the intricate interplay between biological, psychological, and social determinants of pain. Research emphasizes the brain\'s pivotal role in pain perception, underscoring the importance of comprehensive approaches that integrate medical, psychological, and social interventions to address the multifaceted nature of chronic pain in rheumatic diseases effectively.

Chronic pain constitutes a significant disease burden globally and accounts for a substantial portion of healthcare spending. The COVID-19 pandemic contributed to an increase in this burden as patients presented with musculoskeletal or neuropathic pain after contracting COVID-19 or had their chronic pain symptoms exacerbated by the virus. This extensive literature review analyzes the epidemiology of pain pre-pandemic, the costs associated with the COVID-19 pandemic, the impact of the virus on the body, mechanisms of pain, management of chronic pain post-pandemic, and potential treatment options available for people living with chronic pain who have had or are currently infected with COVID-19.

In patients with neck pain, it is unclear whether pain inhibition and facilitation endogenous pain mechanisms are altered. This systematic review and meta-analysis aimed to improve their understanding by assessing conditioned pain modulation (CPM) and temporal summation of pain (TSP) in patients with neck pain associated with whiplash-associated disorders (WAD) or of a nonspecific neck pain (NSNP) nature compared to pain-free controls. Very low certainty evidence suggests: impaired CPM when assessed remotely in chronic WAD patients (n = 7, 230 patients and 204 controls, standardized mean differences (SMD) = -.47 [-.89 to -.04]; P = .04) but not locally (n = 6, 155 patients and 150 controls; SMD = -.34 [-.68 to .01]; P = .05), impaired CPM in chronic NSNP patients when assessed locally (n = 5, 223 patients and 162 controls; SMD = -.55 [-1.04 to -.06]; P = .04) but not remotely (n = 3, 72 patients and 66 controls; SMD = -.33 [-.92 to .25]; P = .13), TSP not facilitated in either chronic WAD (local TSP: n = 4, 90 patients and 87 controls; SMD = .68 [-.62 to 1.99]) (remote TSP: n = 8, 254 patients and 214 controls; SMD = .18 [-.12 to .48]) or chronic NSNP (local TSP: n = 2, 139 patients and 92 controls; SMD = .21 [-1.00 to 1.41]), (remote TSP: n = 3; 91 patients and 352 controls; SMD = .60 [-1.33 to 2.52]). The evidence is very uncertain whether CPM is impaired and TSP facilitated in patients with WAD and NSNP. PERSPECTIVE: This review and meta-analysis present the current evidence on CPM and TSP in patients with WAD and NSNP. Standardization of measurement methodology is needed to draw clear conclusions. Subsequently, future studies should investigate the clinical relevance of these measurements as prognostic variables or predictors of treatment success.

BACKGROUND: People with neuropathic-like symptoms had more unfavourable pain features than people with nociceptive. Moreover, deficient conditioned pain modulation is common in people with neuropathic-like symptoms. PainDETECT questionnaire have been used to assess the central sensitisation sign and symptoms. However, whether the painDETECT questionnaire can identify the conditioned pain modulation\'s impairment is still unknown. Therefore, the current study aimed to evaluate the diagnostic accuracy of the painDETECT questionnaire in detecting the impairment of conditioned pain modulation in people with musculoskeletal pain.
METHODS: We conducted a diagnostic accuracy comparing the painDETECT questionnaire (index method) with the cold pressor test, the psychophysical test used to assess the conditioned pain modulation (reference standard). We determined diagnostic accuracy by calculating sensitivity, specificity, predictive values, and likely hood ratios.
RESULTS: We retrospectively enrolled 308 people with musculoskeletal pain in outpatient departments. Most participants were female (n 20 = 220, 71.4%) and had a mean age of 52.2 (± 15.0) years. One hundred seventy-three (56.1%) participants were classified as nociceptive pain, 69 (22.4%) as unclear, and 66 (21.4%) as neuropathic-like symptoms. According to the cold pressor test, 60 (19.4%) participants presented impairment of conditioned pain modulation. The cutoff point of 12 of the painDETECT questionnaire showed values of diagnostic accuracy below 70% compared to the cold pressor test, except for a negative predictive value [76.9 95% Confidence Interval (CI) 71.7 to 81.5]. The cutoff point 19 showed high specificity (78.6%, 95% CI 73.0 to 83.5), high negative predictive value (80.5%, 95% CI 78.1 to 82.7), and accuracy of 67.5% compared to the cold pressor test.
CONCLUSIONS: The painDETECT questionnaire seems valuable for ruling out people with musculoskeletal pain and impairment of conditioned pain modulation.

Studies suggest that a range of pain mechanisms, such as poor quality of sleep, perceived stress, pain catastrophizing or pain sensitivity, are likely to enhance clinical pain. Animal studies suggest that these pain mechanisms can be modulated by increasing physical activity, but human data are needed to support this hypothesis. This exploratory study aimed to investigate the changes in pain mechanisms after a simple self-directed walking program of 8-weeks. Additionally, this exploratory study investigated the interaction between changes over time in assessments of poor quality of sleep, perceived stress, pain catastrophizing or pain sensitivity and how these changes interacted with each other.
This prospective cohort study included 30 healthy subjects who were assessed at baseline and 4- and 8-weeks after initiating the walking program (30 min walking/day for 8 weeks). Self-report outcomes included: Pain Catastrophizing Scale (PCS), the Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index. Pressure pain thresholds, temporal summation of pain and conditioned pain modulation (CPM) were assessed using cuff algometry.
Twenty-four subjects completed all the visits (age: 42.2, SD: 14.9, 16 females). PCS and PSS significantly decreased at the 8-week\'s visit compared to baseline (p<0.05). No significant differences were seen for an improvement in quality of sleep (p=0.071) and pain sensitivity (p>0.075) when comparing the 8-week\'s visit to the baseline visit. Changes in pain mechanisms comparing baseline and 8-weeks data were calculated and regression analyses found that an improvement in PCS was associated with an improvement in CPM (R2=0.197, p=0.017) and that a higher adherence to the walking program was associated with a larger improvement in PCS (R2=0.216, p=0.013).
The current exploratory study indicates that a simple self-directed walking program of 8-weeks can improve pain catastrophizing thoughts, perceived stress. Higher adherence to the walking program were associated with an improvement in pain catastrophizing and an improvement in pain catastrophizing was associated with an increase in conditioned pain modulation.