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This MONONOFU trial subgroup analysis evaluates the efficacy of lasmiditan across patient and migraine characteristics in Japanese patients with migraine.
Learn More >Neuropathic pain is a common chronic pain, characterized by spontaneous pain and mechanical allodynia. The incidence of neuropathic pain is on the rise due to infections, higher rates of diabetes and stroke, and increased use of chemotherapy drugs in cancer patients. At present, due to its pathophysiological process and molecular mechanism remaining unclear, there is a lack of effective treatment and prevention methods in clinical practice. Now, we use bioinformatics technology to integrate and filter hub genes that may be related to the pathogenesis of neuropathic pain, and explore their possible molecular mechanism by functional annotation and pathway enrichment analysis.
Learn More >Chronic non-specific neck pain (CINP) is common, but the etiology remains unclear. This study aimed to examine the relationship between cervical muscle composition (cervical multifidus and longus capitis/longus colli), morphometry, range of movement, muscle function, and disability severity (Neck Disability Index) in patients with CINP. From September 2020 to July 2021, subjects underwent cervical MRI and clinical tests (cervical range of motion, cranio-cervical flexion test, neck flexor, and extensor muscle endurance). MRI analysis comprised muscle cross-sectional area, volume, and fat infiltration of multifidus and longus colli between C4 and C7 levels. Twenty-five participants were included. Multiple linear regression analysis indicated that NDI was positively correlated with the volume percentage of fat infiltration of the multifidus (B = 0.496), negatively correlated with fat-free muscle volume of the multifidus normalized by subject height (B = -0.230), and accounted for 32% of the variance. There was no relationship between neck disability and longus capitis/longus colli morphology. We also found no relationship between neck disability scores, neck flexor or extensor muscle endurance, or the outcome motor control test of craniocervical flexion ( > 0.05). Neck disability was moderately correlated with the percentage of fat volume in the multifidus muscle and fat-free volume of the multifidus. There was no relationship between NDI scores and muscle function test outcomes or any fat or volume measures pertaining to the longus colli muscle.
Learn More >Open-label placebos, or placebos without deception, have been found to induce analgesia, a challenging concept that need to be investigated in detail. In particular, what we need to know is the mechanism through which analgesia is induced when no deception is involved. Here we show for the first time that open-label placebo analgesia can be reversed by the opioid antagonist naloxone, as already shown for deceptive placebos. To do this, we used the tourniquet technique to induce experimental ischemic arm pain. The open-label placebo challenge started when pain scores reached 7 on a 0-10 rating scale. Whereas 59.4% of the subjects did not respond to the open-label placebo, 40.6% showed a substantial response. On the basis of the natural history control group, a placebo responder reported pain scores equal to or less than 7 after 9 min from the open-label placebo administration. In these responders, we found that a hidden injection of 10 mg naloxone could reverse placebo analgesia compared to a hidden injection of saline solution. At least two control groups showed that naloxone per se was not hyperalgesic, thus ruling out naloxone-induced hyperalgesia as a confounding variable. In light of the need to better understand open-label placebo effects, these findings represent the first experimental evidence that nondeceptive placebo analgesia may be mediated by the same mechanisms as deceptive placebo analgesia, namely, the endogenous opioid systems.
Learn More >People with chronic pain often fear and avoid movements and activities that were never paired with pain. Safe movements may be avoided if they share some semantic relationship with an actual pain-associated movement. The current study investigated whether pain-associated operant responses (movements) can become categorically associated with perceptually dissimilar responses, thus motivating avoidance of new classes of safe movements – a phenomenon known as category-based avoidance generalization. Using a robotic arm, two groups were trained to categorize arm-movements in different ways. Subsequently, the groups learned through operant conditioning, that an arm-movement from one of the categories was paired with a high probability of pain, while the others were paired with either a medium probability, and no pain (acquisition phase). Self-reported pain-related fear and pain-expectancy were collected as indices of fear learning. During a final generalization test phase, the movements categorically related to those from the acquisition phase were made available but in the absence of pain. Results showed that the generalization of outcome measures depended on the categorical connections between arm-movements, that is, the groups avoided and feared the novel generalization movement categorically related to the pain-associated acquisition movement, depending on how they had previously learned to categorize the movements. This suggests that operant pain-related avoidance can generalize to safe behaviors, which are not perceptually, but categorically, similar to a pain-associated behavior. This form of pain-related avoidance generalization is problematic because category-based relations can be extremely wide reaching and idiosyncratic. Thus, category-based generalization of operant pain-related avoidance merits further investigation.
Learn More >Neurotoxic chemotherapy has been shown to be associated with reduced corneal nerves and ocular surface discomfort. Substance P is a neuropeptide expressed by sensory nerves including those in the densely innervated cornea. It is involved in both pain signaling and the regulation of epithelial and neural health. While its levels in tear fluids have been used as a neuropathic biomarker in diabetes, investigations of tear concentrations of substance P in chemotherapy-induced peripheral neuropathy have not been explored. The current cross-sectional study assessed substance P expression in tears of patients following neurotoxic chemotherapy treatment. Patients treated with paclitaxel (n = 35) or oxaliplatin (n = 30) 3-24 months prior to assessment were recruited along with healthy controls (n = 25). Flush tear collection, in-vivo corneal confocal microscopy and neurotoxicity assessments were also conducted. Enzyme-linked immunosorbent assays were used to measure substance P concentrations in collected tears, while total protein content (TPC) was measured with the bicinchoninic acid method (BCA). General linear models were used for statistical analysis. Substance P concentration was reduced in paclitaxel-treated patients [Median (Interquartile range, IQR): 1.11 (0.20-2.24) ng/ml)] compared to the oxaliplatin group [4.28 (1.01-10.73) ng/ml, p = 0.02]. Substance P expressed as a proportion of TPC was also lower in the paclitaxel group [0.00006 (0.00001-0.00010) %] compared to the oxaliplatin group [0.00018 (0.00008-0.00040) %, p = 0.005]. Substance P concentration and its percentage in TPC were also reduced in the paclitaxel group when compared to healthy controls [4.61 (1.35-18.51) ng/ml, p = 0.02; 0.00020 (0.00006-0.00060) %, p = 0.04, respectively]. Higher cumulative dose of paclitaxel was correlated with a reduction in substance P concentrations (r = -0.40, p = 0.037), however no associations were found with corneal nerve parameters or neuropathy severity (p > 0.05). While these findings show evidence for the dysregulation of tear film substance P following paclitaxel treatment, longitudinal studies should be conducted to investigate how substance P levels in tears change during treatment.
Learn More >(1) Background: It is essential to focus attention on sex-specific factors which are clinically relevant in pain management, especially with regards to opioid use disorder (OUD) risk. The aim of this study was to explore potential sex-differences in chronic non-cancer pain (CNCP) outpatients. (2) Methods: An observational cross-sectional study was conducted under CNCP outpatients with long-term prescribed opioids ( = 806), wherein 137 patients had an OUD diagnosis (cases, 64% females) and 669 did not (controls, 66% females). Socio-demographic, clinical, and pharmacological outcomes were analyzed. (3) Results: Female controls presented an older age and less intensive pain therapy but higher psychotropic prescriptions and emergency department visits compared to male controls. Meanwhile, cases demonstrated a younger age, higher work disability, double morphine equivalent daily dose, and benzodiazepine use compared with controls. Here, female cases showed an 8% greater substance use disorder (OR 2.04 [1.11-3.76]) and 24% lower tramadol use, while male cases presented a 22% higher fentanyl use (OR 2.97 [1.52-5.81]) and reported the highest number of adverse drug reactions (24%, OR 2.40 [1.12-5.16]) compared with controls. (4) Conclusions: An OUD individual risk profile was evidenced with sex-differences to take into consideration to design equal prevention programs.
Learn More >Nowadays, there is evidence that relates the amount of physical activity, as well as the impact of psychological factors, to the intensity of symptoms present in patients with fibromyalgia (FM). However, there are no studies which correlate the level of association of physical activity, psychological factors and vegetative symptoms in the FM population. The study has a cross-sectional observational design with 41 participants being recruited from a private clinic and rehabilitation service. The Autonomic Symptom Profile (Compass-31) to assess vegetative symptoms, the GODIN questionnaire to evaluate the level of leisure activity, and the pain catastrophizing scale, Tampa Kinesiophobia Scale and Self-Efficacy Scale to assess psychological factors, were used. A low and significant level of association was found between pain catastrophizing (PCS) and Kinesiophobia (r = 0.398; < 0.01), as well as with catastrophizing and vegetative symptoms (r = 0.428; < 0.05). Furthermore, a low and significant level of association was also found between self-efficacy and vegetative symptoms (r = 0.397; < 0.05). No association was found between the level of daily physical activity (measured by the Godin Leisure questionnaire) and vegetative symptoms, nor with any psychological factor studied. There is an association between vegetative symptoms and psychological factors. Nevertheless, more research which takes other factors into account, such as lifestyle and nutritional, is needed.
Learn More >Back and low back pain have been reported as one of the leading causes of activity restriction. While degenerative changes in the spine are among the common causes of low back pain, zygapophyseal (facet) joint pain is seen as the most widely accepted cause of back pain. Standard imaging modalities may have low predictive value in detecting the source of back pain. Thanks to radionuclide bone scintigraphy, painful lesions can be distinguished from age-related changes, especially in patients with chronic low back pain. In this study, we aimed to retrospectively evaluate the clinical results of facet-induced low back pain, which was confirmed by bone scintigraphy, after facet injection treatment.
Learn More >Fear-avoidance models of chronic pain consider excessive spreading (or overgeneralization) of pain-related avoidance toward safe activities to play a crucial role in chronic pain disability. This study (N = 96) investigated whether avoidance generalization is mitigated by positive affect induction. Pain-free, healthy participants performed an arm-reaching task during which certain movements were followed by pain, while another was not. One group then performed an exercise to induce positive affect (positive affect group), while another group performed a neutral exercise (neutral group). A third group also performed the neutral exercise, but did not learn to avoid pain during the arm-reaching task (yoked neutral group). To test generalization, we introduced novel but similar movements that were never followed by pain in all groups. Results showed no differences in generalization between the positive affect and neutral groups; however, across groups, higher increases in positive affect were associated with less generalization of avoidance, and less generalization of pain-expectancy and pain-related fear. Compared to the yoked neutral group, the neutral group showed avoidance generalization, as well as pain-expectancy and pain-related fear generalization. These results point toward the potential of positive affect interventions in attenuating maladaptive spreading of pain-related avoidance behavior to safe activities.
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