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The endogenous opioid and cannabinoid receptor systems are widely distributed and co-localized throughout central and peripheral nervous system regions. A large body of preclinical evidence suggests that there are functional interactions between these two systems that may be leveraged to address various health conditions. Numerous animal studies have shown that cannabinoid agonists (e.g., delta-9-tetrahydrocannabinol [Δ-THC]) enhance the analgesic effects of µ-opioid analgesics as evidenced by decreasing the opioid dose required for analgesia (i.e., opioid sparing) and extending the duration of the opioid analgesia. In contrast, controlled human laboratory studies and clinical trials have not demonstrated robust analgesic or opioid-sparing effects from opioid-cannabinoid combinations. Meta-analyses of the literature (clinical trials, controlled laboratory studies; some non-controlled studies/case reports) have examined the effects of cannabis/cannabinoids for pain relief in those taking a wide variety of analgesics, including prescription opioid medications. These data do not strongly support the use of cannabinoids for chronic pain nor do prospective studies demonstrate significant cannabinoid-mediated opioid-sparing effects. Preclinical studies have also suggested a role for cannabinoids for the treatment of opioid withdrawal. Controlled laboratory and clinical studies suggest that there may be a modest signal for Δ-THC to suppress some opioid signs and symptoms but they are not completely ameliorated and there may also be concerns around safety of Δ-THC administration in a state of heightened autonomic arousal as occurs with opioid withdrawal. Despite anecdotal and correlational reports suggesting a benefit of cannabis on reducing opioid overdose, there is no strong data supporting this contention and emerging reports have conflicting results. In summary, there is a groundswell of public advocacy supporting the use of cannabis and cannabinoids to replace opioid analgesics or to reduce opioid use; however, the extant controlled clinical data do not support the role of cannabinoids for opioid replacement or opioid-sparing effects when treating opioid use disorder or chronic pain.
Learn More >Migraine is a burdensome disease with an especially high prevalence in women between the age of 15 and 49 years. Non-pharmacological, non-invasive therapeutic methods to control symptoms are increasingly in demand to complement a multimodal intervention approach in migraine. Thirty-seven subjects (age: 25.0 ± 4.1 years; 36 females) diagnosed with high-frequency episodic migraine who presented at least one active myofascial trigger point (mTrP) in the trapezius muscles and at least one latent mTrP in the deltoid muscles bilaterally prospectively underwent six sessions of repetitive peripheral magnetic stimulation (rPMS) over two weeks. Patients were randomly assigned to receive rPMS applied to the mTrPs of the trapezius (n = 19) or deltoid muscles (n = 18). Whereas the trapezius muscle is supposed to be part of the trigemino-cervical complex (TCC) and, thus, involved in the pathophysiology of migraine, the deltoid muscle was not expected to interfere with the TCC and was therefore chosen as a control stimulation site. The headache calendar of the German Migraine and Headache Society (DMKG) as well as the Migraine Disability Assessment (MIDAS) questionnaire were used to evaluate stimulation-related effects. Frequency of headache days decreased significantly in both the trapezius and the deltoid group after six sessions of rPMS (trapezius group: p = 0.005; deltoid group: p = 0.003). The MIDAS score decreased significantly from 29 to 13 points (p = 0.0004) in the trapezius and from 31 to 15 points (p = 0.002) in the deltoid group. Thus, rPMS applied to mTrPs of neck and shoulder muscles offers a promising approach to alleviate headache frequency and symptom burden. Future clinical trials are needed to examine more profoundly these effects, preferably using a sham-controlled setting.
Learn More >Current literature lacks data-driven guidelines for surgical treatments of adolescents and young adults (AYAs) with chronic pelvic pain. We hypothesized that there is a significant variation in treatment of these patients, which may be an indicator of over or under treatment by some providers.
Learn More >Background and aims A multimodal rehabilitation programme (MMRP) is an evidence-based treatment of chronic pain conditions. The complexity involved in chronic pain needs to be identified and evaluated in order to adapt the rehabilitation to patients' needs. The aim was to investigate the multivariate relationships between self-reported variables in patients with chronic pain before taking part in MMRP in primary care, with a special focus on gender and degree of sick leave. Methods Prior to MMRP, 397 patients (339 women and 58 men) filled in a questionnaire about pain, healthcare aspects, health-related quality of life, anxiety and depression, coping, physical function, and work-related variables e.g. sick leave. Data were analysed by principal component analysis (PCA) and partial least square analysis. Results The PCA identified four components that explained 47% of the variation in the investigated data set. The first component showed the largest variation and was primarily explained by anxiety and depression, quality of life, acceptance (activity engagement), and pain-related disability. Gender differences were only seen in one component with the pain variables having the highest loadings. Degree of sick leave was not well explained by the variables in the questionnaire. Conclusions The questionnaire filled out by the patients prior to participation in MMRP in primary care identified much of the complexity of chronic pain conditions but there is room for improvement, e.g. regarding explanation of work-related factors. In the multivariate analysis, gender did not fall out as an important factor for how most patients answered the questions. Implications There are not many studies that describe patients who undergo MMRP in primary care since previously such patients were treated mostly in specialist care. More knowledge is needed about these patients in order to improve rehabilitation plans and interventions. The results suggest that the questionnaire identifies the complexity among chronic pain patients in primary care. The identified components could improve assessment before MMRP and contribute to better tailored programmes.
Learn More >Ongoing pain is one of the most common diseases and has major physical, psychological, social, and economic impacts. A mobile health intervention utilizing a fully automated text-based health care chatbot (TBHC) may offer an innovative way not only to deliver coping strategies and psychoeducation for pain management but also to build a working alliance between a participant and the TBHC.
Learn More >Itch in atopic dermatitis (AD) is aggravated under warm conditions. Transient receptor potential vanilloid 3 (TRPV3), a member of the thermosensitive TRP channels, is activated by innocuous heat and is abundantly expressed in keratinocytes. The potential role of TRPV3 in itch is illustrated in TRPV3 channelopathies of human and mice. However, the role of TRPV3 in heat-induced itch in AD and the underlying mechanisms are unclear. Here we showed that keratinocytes isolated from patients with AD exhibit enhanced expression and heat sensitivity with hyperactive channel function of TRPV3. Heat stimulus induced enhanced secretion of thymic stromal lymphopoietin (TSLP), nerve growth factor (NGF), and prostaglandin E2 (PGE2) by keratinocytes from AD patients via TRPV3 activation. TRPV3 agonists increased TSLP, NGF, PGE2, and IL-33 production in human keratinocytes and induced scratching behavior upon intradermal injection in mice. TRPV3 was upregulated in the skin of MC903-induced AD mouse model. Heat stimulation to MC903-treated mice increased scratching behavior and produced higher levels of TSLP, NGF, PGE2, and IL-33 from epidermis, which were attenuated by pharmacological inhibition of TRPV3. Moreover, neutralization of TSLP reduced heat-evoked scratching in MC903-challenged mice. These results suggest that TRPV3 is a potential therapeutic target for heat-induced itch in AD.
Learn More >Multimorbidity and pain are both common among older adults, yet pain treatment strategies for older patients with multimorbidity have not been well characterized. To assess the prevalence and relationship between multimorbidity and opioid prescribing in hospitalized older medical patients with pain. We collected demographic, morbidity, pain, and analgesic treatment data through structured review of the electronic medical records of a consecutive sample of 238 medical patients, aged ≥65 years admitted between November 2014 and May 2015 with moderate-to-severe pain by numerical pain rating scale (range 4-10). We used the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) to assess multimorbidity and cumulative illness burden. We examined the relationship between morbidity measures and opioid prescribing at hospital discharge using multivariate regression analysis. The mean age was 75 ± 8 years, 57% were female and 50% were non-White. Mean CIRS-G total score was 17 ± 6, indicating high cumulative illness burden. Ninety-nine percent of patients had multimorbidity, defined as moderate-to-extremely severe morbidity in ≥2 organ systems. Sixty percent of patients received an opioid prescription at discharge. In multivariate analyses adjusted for age, race, and gender, patients with a discharge opioid prescription were significantly more likely to have higher cumulative illness burden and chronic pain. Among older medical inpatients, multimorbidity was nearly universal, and patients with higher cumulative illness burden were more likely to receive a discharge opioid prescription. More studies of benefits and harms of analgesic treatments in older adults with multimorbidity are needed to guide clinical practice.
Learn More >Individual differences in emotional functioning, pain appraisal processing, and perceived social support may play a relevant role in the subjective experience of pain. Due to the paucity of data regarding individuals with Rheumatoid Arthritis (RA), the present study aimed to examine pain intensity, emotional functioning (psychological distress and alexithymia), pain appraisal (pain beliefs, pain catastrophizing, and pain-related coping strategies) and social support, and their relationships with the health-related quality of life (HRQoL) in patients with RA. Data were collected from 108 female patients diagnosed with RA. Clinically relevant levels of depressive and anxiety symptoms assessed by the HADS subscales were present in 34% and 41% of the patients, respectively, and about 24% of them exhibited the presence of alexithymia. The results of hierarchical multiple regression analyses showed that pain intensity, alexithymia, the maladaptive beliefs regarding the stability of pain and the coping strategy of guarding explained 54% of the variance in the physical component of HRQoL (p < 0.001). Depression subscale of the HADS, alexithymia, the coping strategy of resting, and the rumination factor of pain catastrophizing significantly explained 40% of the variance in the mental component of HRQoL (p < 0.001). The present findings provide evidence regarding the importance of emotional functioning and pain appraisal in the negative impact of RA on patients' quality of life. These findings provide additional evidence for the biopsychosocial model of chronic pain, further supporting the complex interaction between emotional, cognitive, and behavioral processes in patients with chronic pain.
Learn More >Stasis dermatitis (SD) is a common disease in the elderly population, with pruritus being one of the bothersome symptoms. However, there are few therapeutic modalities available for SD-associated itch because little is known about its pathophysiological mechanism. Therefore, we sought to investigate the mediators of itch in SD using an immunofluorescence study on patient lesions focusing on IL-31. Ex vivo stimulation studies using murine peritoneal macrophages were also used to elucidate the pathological mechanisms of IL-31 generation. In SD lesions, dermal infiltrating IL-31(+) cells were increased in number compared to healthy controls, and the majority of IL-31(+) cells were CD68(+) macrophages. The presence of itch in SD was significantly associated with the amount of CD68(+)/IL-31(+) macrophages and CD68(+)/CD163(+) M2 macrophages. The number of CD68(+)/IL-31(+) macrophages was correlated with the number of dermal CCR4(+) Th2 cells, IL-17(+) cells, basophils, substance P(+) cells, and dermal deposition of periostin and hemosiderin. Furthermore, murine peritoneal macrophages expressed an M2 marker arginase-1 and generated IL-31 when stimulated with a combination of substance P, periostin, and red blood cell lysate (representing hemosiderin). IL-31 from macrophages may play a role in itch in SD.
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