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The cytokine, interleukin-23 (IL-23), can be critical for the progression of inflammatory diseases, including arthritis, and is often associated with T lymphocyte biology. We previously showed that certain lymphocyte-independent, inflammatory arthritis and pain models have a similar requirement for tumour necrosis factor (TNF), granulocyte macrophage-colony stimulating factor (GM-CSF), and C-C motif ligand 17 (CCL17). Given this correlation in cytokine requirements, we explored whether IL-23 might interact with this cytokine cluster in the control of arthritic and inflammatory pain.
Learn More >The autoimmune disease rheumatoid arthritis (RA) affects approximately 1% of the global population. RA is characterized with chronic joint inflammation and often associated with chronic pain. The imbalance of pro-inflammatory and anti-inflammatory macrophages is a feature of RA progression. Glial cells affecting neuronal sensitivity at both peripheral and central levels may also be important for RA progression and associated pain. Genetic variants in the T cell death-associated gene 8 (TDAG8) locus are found to associate with spondyloarthritis. TDAG8 was also found involved in RA disease progression and associated hyperalgesia in the RA mouse model. However, its modulation in RA remains unclear.
Learn More >Our aim was to investigate the relationship between coexisting cluster headache (CH) and migraine with anxiety and depression during active cluster bouts, and how symptoms change during remission.
Learn More >There is histological evidence of microstructural changes in the zygomaticotemporal branch of the trigeminal nerve in migraineurs. This raises the possibility that altered trigeminal nerve properties contribute to migraine pathophysiology. Whilst it is not possible to explore the anatomy of small trigeminal nerve branches it is possible to explore the anatomy of the trigeminal root entry zone using magnetic resonance imaging in humans. The aim of this investigation is to assess the microstructure of the trigeminal nerve in vivo to determine if nerve alterations occur in individuals with episodic migraine.
Learn More >Pain is a source of substantial discomfort. Abnormal activity in both the zona incerta (ZI) and posterior complex of the thalamus (Po) are implicated in neuropathic pain, but their exact roles remain unclear. In particular, the precise cell types and molecular mechanisms of the ZI-Po circuit that regulate nociception are largely uncharacterized. Here, we found that parvalbumin (PV)-positive neuronal projections from the ventral ZI (ZIv) to the Po (ZIv-Po) are critical for promoting nocifensive behaviors, whereas selectively inhibiting ZIv-Po activity reduces nocifensive withdrawal responses. Furthermore, cannabinoid type 1 receptors (CBRs) are expressed specifically at ZIv-Po axon terminals in this circuit, and cannabinoids attenuate nocifensive responses through presynaptic inhibition. Selective inhibition of the ZIv-Po circuit or administration of cannabinoids into the Po are sufficient to ameliorate pathological pain. These findings identify the critical role of the ZIv-Po circuit and its modulation by endocannabinoids in controlling nocifensive behaviors.
Learn More >The effectiveness of Spinal Cord Stimulation (SCS) as pain-relieving treatment for Failed Back Surgery Syndrome (FBSS) has already been demonstrated. However, potential structural and functional brain alterations resulting from subsensory SCS are less clear. The aim of this study is to test structural volumetric changes in a priori chosen regions of interest related to chronic pain after 1 month and 3 months of high-frequency SCS, in patients with FBSS.
Learn More >Chronic pain is a significant health problem worldwide with limited pharmacological treatment options. This study evaluated the relative efficacy of four treatment sessions each of four non-pharmacological treatments: (1) hypnotic cognitive therapy (using hypnosis to alter the meaning of pain); (2) standard cognitive therapy; (3) hypnosis focused on pain reduction, and (4) pain education. One hundred seventy-three individuals with chronic pain were randomly assigned to receive four sessions of one of the four treatments. Primary (pain intensity) and secondary outcome measures were administered by assessors unaware of treatment allocation at pre-treatment, post-treatment, and 3-, 6- and 12-month follow-up. Treatment effects were evaluated using ANOVA, a generalized estimating equation approach, or a Fisher Exact Test, depending on the outcome domain examined. All four treatments were associated with medium to large effect size improvements in pain intensity that maintained up to 12 months post-treatment. Pre- to post-treatment improvements were observed across the four treatment conditions on the secondary outcomes of pain interference and depressive symptoms, with some return towards pre-treatment levels at 12-months follow-up. No significant between group differences emerged in omnibus analyses, and few statistically significant between-group differences emerged in the planned pairwise analyses, although the two significant effects that did emerge favored hypnotic cognitive therapy. Future research is needed to determine if the significant differences that emerged are reliable.
Learn More >Background and aims A considerable research-literature focuses on pain during labor and associations with postpartum persistent pain and depression, with findings pointing in various directions. The aim of this study was to examine the role of labor pain and overall birth experience in the development of pain and depression 8 weeks after delivery. Methods The study sample was drawn from the Akershus Birth Cohort. Data from multiple sources were used, including the hospital's birth record (n = 4,391), questionnaire data from gestational week 17 of pregnancy (n = 3,752), 8 weeks postpartum (n = 2,217), and two questions about pain and birth experience asked within 48 h after delivery (n = 1,221). The Edinburgh Postnatal Depression Scale was used to measure postpartum depression, a single question was used to measure persistent pain 8 weeks postpartum, while pain and birth experience were measured by numeric rating scales. A history of pre-pregnant depression and chronic pain were measured through self-report questions in gestational week 17. A total of 645 women had complete data from all sources. We applied multiple imputation techniques to handle missing responses on the two questions about pain and birth experience. Results The results showed that neither labor pain nor birth experience were associated with persistent pain 8 weeks postpartum, whereas pain before pregnancy (OR 3.70; 95% CI 2.71-5.04) and a history of depression (OR 2.31; 95% CI 1.85-2.88) were statistically significant predictors of persistent pain. A negative birth experience was significantly (OR 1.16; 95% CI 1.04-1.29) associated with postpartum depression, whereas labor pain intensity was not. A history of depression (OR 3.95; 95% CI 2.92-5.34) and pre-pregnancy pain (OR 2.03; 95% CI 1.37-3.01) were important predictors of postpartum depression 8 weeks after delivery. Conclusions and implications Whilst the relationship between labor pain intensity and postpartum pain and depression remain unclear, our results do imply the need to screen for previous depression and chronic pain conditions in pregnant women, as well as consider preventive measures in those who screen positive.
Learn More >Classical Ehlers-Danlos syndrome (cEDS) is a connective tissue disorder caused by heterozygous mutations in one of the type V collagen-encoding genes, COL5A1 or COL5A2. cEDS is characterized by generalized joint hypermobility and instability, hyperextensible, fragile skin and delayed wound healing. Chronic pain is a major problem in cEDS patients, but the underlying mechanisms are largely unknown, and studies in animal models are lacking. Therefore, we assessed pain-related behaviors in haploinsufficient Col5a1 mice, which clinically mimic human cEDS. Compared to wild-type (WT) littermates, 15-20 week-old Col5a1 mice of both sexes showed significant hypersensitivity to mechanical stimuli in the hind paws and the abdominal area, but responses to thermal stimuli were unaltered. Spontaneous behaviors, including distance travelled and rearing, were grossly normal in male Col5a1 mice, while female Col5a1 mice showed altered climbing behavior. Finally, male and female Col5a1 mice vocalized more than WT littermates when scruffed. Decreased grip strength was also noted. In view of the observed pain phenotype Col5a1 mice were crossed with NaV1.8-tdTomato reporter mice, enabling visualization of nociceptors in the glabrous skin of the footpad. We observed a significant decrease in intra-epidermal nerve fiber density, with fewer nerves crossing the epidermis, and a decreased total nerve length of Col5a1 mice compared to WT. In summary, male and female Col5a1 mice show hypersensitivity to mechanical stimuli, indicative of generalized sensitization of the nervous system, in conjunction with an aberrant organization of cutaneous nociceptors. Therefore, Col5a1 mice will provide a useful tool to study mechanisms of pain associated with cEDS.
Learn More >Abdominal pain-predominant functional gastrointestinal disorders encompass a group of chronic conditions featuring abdominal pain where no serious gastrointestinal or intra-abdominal pathology is present. The Rome IV classification system defines and categorises this group based on symptomatology as: functional dyspepsia, irritable bowel syndrome, functional abdominal pain – not otherwise specified and abdominal migraine. These conditions can impact the functioning of the child and family significantly and are challenging to manage. Although the causes of these conditions are not clear, recent years have seen an improved understanding of underlying pathophysiology and identification of effective management options for these conditions.
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