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Data are equivocal on the consequences of COVID-19 pandemic on pain and well-being for individuals with chronic pain. Furthermore, little is known regarding its impact on the health of young adults with chronic pain. We conducted a longitudinal study to compare pain, psychological functioning, and substance use before and during the pandemic of 196 young adults with chronic pain. Participants aged 18 to 24 years (M = 21.1 years; 79.6% females) reported on pain, anxiety, depression, and substance use before (October 2018-August 2019) and during the pandemic (October 2020-November 2020), in addition to the assessment of COVID-19 exposure and its impact. Before the pandemic, young adults experienced mild-to-moderate pain intensity (M = 3.75, SD = 2.33) and pain interference (M = 3.44, SD = 2.69). Findings were that pain intensity, pain interference, and depression symptoms remained stable during the pandemic. In contrast, anxiety symptoms increased significantly (M = 8.21, SD = 5.84 vs M = 8.89, SD = 5.95, P = 0.04). Tobacco, alcohol, and cannabis use were unchanged. Mixed linear models revealed that COVID-19 exposure and impact were not associated with changes in pain intensity or interference, with female sex associated with increased pain intensity (β = 0.86, P = 0.02) and pain interference (β = 0.87, P = 0.02). Our findings indicated relative stability of pain symptoms experienced by young adults with chronic pain. However, the increases in anxiety highlight the need to facilitate treatment access for mental health services to mitigate downstream impact.
Learn More >Oral over-the-counter (OTC) analgesics such as acetaminophen, aspirin, ibuprofen, and naproxen sodium are widely used to treat pain. Although generally considered safe, inappropriate use can lead to injury.
Learn More >The opioid use disorder is an international public health problem. Over the past 20 years it has been the subject of numerous publications concerning patients treated for chronic pain other than cancer-related. Patients with cancer-related pain are also at risk of opioid use disorder. The primary objective of this literature review was to determine the prevalence of opioid use disorder in patients with cancer-related chronic pain. Its secondary objective was to identify the characteristics of these opioid users.
Learn More >A newly developed specialized psychosocial aftercare program (PAC) for pediatric patients with chronic pain following an intensive interdisciplinary pain treatment (IIPT) was found to be significantly more effective than IIPT alone. This qualitative study aimed to gain further insight into the mechanisms and prerequisites for the effectiveness of this specialized aftercare program. We conducted structured telephone interviews with patients, parents, and health care professionals conducting PAC. A total of 16 interviews were conducted-seven interviews with parents, six interviews with patients, and three interviews with health care professionals-and transcribed verbatim. Data were analyzed using reflexive thematic analysis. Four major themes consisting of 20 subcategories were identified, namely (1) frame conditions, (2) person factors, (3) stabilization and (4) catalyst. The foundations of treatment success are frame conditions, such as flexibility or constancy, and person factors, such as respect or expertise. Based on these foundations, stabilization is achieved through security, mediation, orientation and support. Altogether, these components of PAC reveal their potential as catalysts for further improvement even after discharge from IIPT. Overall, patients and their families emphasized widespread personal relevance and acceptance of the PAC program. The findings of this study may be employed in the development of other aftercare programs or interventions involving families in the context of psychotherapeutic and psychosocial health care.
Learn More >Osteoarthritis (OA) is the most common degenerative joint disease and a major cause of age-related disability worldwide, mainly due to pain, the disease's main symptom. Although OA was initially classified as a non-inflammatory joint disease, recent attention has been drawn to the importance of synovitis and fibroblast-like synoviocytes (FLS) in the pathogenesis of OA. FLS can be divided into two major populations: thymus cell antigen 1 (THY1)- FLS are currently classified as quiescent cells and assumed to destroy bone and cartilage, whereas THY1+ FLS are invasively proliferative cells that drive synovitis. Both THY1- and THY1+ FLS share many characteristics with fibroblast-like progenitors – mesenchymal stromal cells (MSC). However, it remains unclear whether synovitis-induced metabolic changes exist in FLS from OA patients and whether metabolic differences may provide a mechanistic basis for the identification of approaches to precisely convert the pathologically proliferative synovitis-driven FLS phenotype into a healthy one. To identify novel pathological mechanisms of the perpetuation and manifestation of OA, we analyzed metabolic, proteomic, and functional characteristics of THY1+ FLS from patients with OA. Proteome data and pathway analysis revealed that an elevated expression of pyruvate dehydrogenase kinase (PDK) 3 was characteristic of proliferative THY1+ FLS from patients with OA. These FLS also had the highest podoplanin (PDPN) expression and localized to the sublining but also the lining layer in OA synovium in contrast to the synovium of ligament trauma patients. Inhibition of PDKs reprogrammed metabolism from glycolysis towards oxidative phosphorylation and reduced FLS proliferation and inflammatory cytokine secretion. This study provides new mechanistic insights into the importance of FLS metabolism in the pathogenesis of OA. Given the selective overexpression of PDK3 in OA synovium and its restricted distribution in synovial tissue from ligament trauma patients and MSC, PDKs may represent attractive selective metabolic targets for OA treatment. Moreover, targeting PDKs does not affect cells in a homeostatic, oxidative state. Our data provide an evidence-based rationale for the idea that inhibition of PDKs could restore the healthy THY1+ FLS phenotype. This approach may mitigate the progression of OA and thereby fundamentally change the clinical management of OA from the treatment of symptoms to addressing causes.
Learn More >Increasing evidence suggests that migraine may be the result of an impaired brain glucose metabolism. Several studies have reported brain mitochondrial dysfunction, impaired brain glucose metabolism and gray matter volume reduction in specific brain areas of migraineurs. Furthermore, peripheral insulin resistance, a condition demonstrated in several studies, may extend to the brain, leading to brain insulin resistance. This condition has been proven to downregulate insulin receptors, both in astrocytes and neurons, triggering a reduction in glucose uptake and glycogen synthesis, mainly during high metabolic demand. This scoping review examines the clinical, epidemiologic and pathophysiologic data supporting the hypothesis that abnormalities in brain glucose metabolism may generate a mismatch between the brain's energy reserve and metabolic expenditure, triggering migraine attacks. Moreover, alteration in glucose homeostasis could generate a chronic brain energy deficit promoting migraine chronification. Lastly, insulin resistance may link migraine with its comorbidities, like obesity, depression, cognitive impairment and cerebrovascular diseases. Perspective: Although additional experimental studies are needed to support this novel "neuroenergetic" hypothesis, brain insulin resistance in migraineurs may unravel the pathophysiological mechanisms of the disease, explaining the migraine chronification and connecting migraine with comorbidities. Therefore, this hypothesis could elucidate novel potential approaches for migraine treatment.
Learn More >Chronic pain development is a frequent outcome of severe stressor exposure, with or without tissue injury. Enduring stress-induced hyperalgesia (ESIH) is believed to play a central role, but the precise mechanisms mediating the development of chronic posttraumatic pain, and the time-dependency of these mechanisms, remain poorly understood. Clinical and pre-clinical data suggest that the inhibition of FK506-binding protein 51 (FKBP51), a key stress system regulator, might prevent ESIH. We evaluated whether peritraumatic inhibition of FKBP51 in an animal model of traumatic stress exposure, the single prolonged stress (SPS) model, reversed ESIH evaluated via daily mechanical von Frey testing. FKBP51 inhibition was achieved using SAFit2, a potent and specific small molecule inhibitor of FKBP51, administered to male and female Sprague-Dawley rats via intraperitoneal injection. To assess timing effects, FKBP51 was administered at different times relative to stress (SPS) exposure. SAFit2 administration immediately after SPS produced a complete reversal in ESIH lasting >7d. In contrast, SAFit2 administration 72h following SPS produced only temporary hyperalgesia reversal, and administration 120h following SPS had no effect. Similarly, animals undergoing SPS together with tissue injury (plantar incision) receiving SAFit2 immediately post-surgery developed acute hyperalgesia but recovered by 4d and did not develop ESIH. These data suggest that (1) FKBP51 plays an important, time-dependent role in ESIH pathogenesis, (2) time windows of opportunity may exist to prevent ESIH via FKBP51 inhibition after traumatic stress, with or without tissue injury, and (3) the use of inhibitors of specific pathways may provide new insights into chronic post-traumatic pain development.
Learn More >Transcranial magnetic stimulation (TMS) is an FDA approved treatment for major depression, migraine, obsessive compulsive disorder, and smoking addiction. TMS has gained popular media support, but media coverage and commercial reporting of TMS services may be contributing to the landscape of ethical issues.
Learn More >Transcutaneous electrical nerve stimulation (TENS) uses endogenous opioids to produce analgesia, and effectiveness can be reduced in opioid-tolerant individuals. We examined TENS effectiveness (primary aim), and differences in fibromyalgia symptoms (secondary aim), in women with fibromyalgia regularly taking opioid (RTO) medications compared with women not- regularly taking opioids (not-RTO). Women (RTO n=79; not-RTO not-n=222) with fibromyalgia with daily pain levels ≥4 were enrolled and categorized into RTO (taking opioids at least 5 of 7 days in last 30 days) or not-RTO groups. For the RTO group, participants were categorized into tramadol n=52 (65.8%) and other opioids n=27 (34.2%). Participants were phenotyped across multiple domains including demographics, fibromyalgia characteristics pain, fatigue, sleep, psychosocial factors, and activity. Participants were randomized to active TENS (n=101), placebo TENS (n=99), or no TENS (n=99) for 1-month with randomization stratified by opioid use. Active TENS was equally effective in movement-evoked pain in those in the RTO and not-RTO groups. Women with fibromyalgia in the RTO group were older (p=0.002), lower income (p=0.035), more likely to smoke (p=0.014), and more likely to report depression (p=0.013), hypertension (p=0.005) or osteoarthritis (p=0.027). The RTO group demonstrated greater bodily pain on SF-36 (p=0.005), lower quality of life on the physical health component of the SF-36 (p=0.040), and greater fatigue (MAF-ADL p=0.047; fatigue with sit to stand test (p=0.047) These differences were small of and unclear clinical significance. In summary, regular use of opioid analgesics does not interfere with effectiveness of TENS for movement-evoked pain. Clinical Trial Registration Number: NCT01888640 Perspective: Individuals treated with mixed frequency TENS at strong but comfortable intensity that were taking prescription opioid analgesics showed a significant reduction in movement-evoked pain and fatigue. These data support the use of TENS, using appropriate parameters of stimulation, as an intervention for individuals with fibromyalgia taking opioid analgesics.
Learn More >Neuropathic pain in rodents can be driven by ectopic spontaneous activity (SA) generated by sensory neurons in dorsal root ganglia (DRG). The recent demonstration that SA in dissociated human DRG neurons is associated with reported neuropathic pain in patients enables detailed comparison of pain-linked electrophysiological alterations driving SA in human DRG neurons to alterations that distinguish SA in nociceptors from SA in low-threshold mechanoreceptors (LTMRs) in rodent neuropathy models. Analysis of recordings from dissociated somata of patient-derived DRG neurons showed that SA and corresponding pain in both sexes were significantly associated with the three functional electrophysiological alterations sufficient to generate SA in the absence of extrinsic depolarizing inputs. These include enhancement of depolarizing spontaneous fluctuations of membrane potential (DSFs), which were analyzed quantitatively for the first time in human DRG neurons. The functional alterations were indistinguishable from SA-driving alterations reported for nociceptors in rodent chronic pain models. Irregular, low-frequency DSFs in human DRG neurons closely resemble DSFs described in rodent nociceptors while differing substantially from the high-frequency sinusoidal oscillations described in rodent LTMRs. These findings suggest that conserved physiological mechanisms of SA in human nociceptor somata can drive neuropathic pain despite documented cellular differences between human and rodent DRG neurons. Perspective: Electrophysiological alterations in human sensory neurons associated with patient-reported neuropathic pain include all three of the functional alterations that logically can promote spontaneous activity. The similarity of distinctively altered spontaneous depolarizations in human DRG neurons and rodent nociceptors suggests that spontaneously active human nociceptors can persistently promote neuropathic pain in patients.
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