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New daily persistent headache (NDPH) is a subset of chronic headache where the pain is continuous from onset. Phenotypically it has chronic migraine or chronic tension type features. NDPH is considered to be highly refractory. Occipital nerve stimulation (ONS) has been used for treatment of refractory chronic migraine but there are no specific reports of its use for NDPH with migrainous features.
Learn More >We aimed at evaluating the differential involvement of large myelinated Aβ-fibers, small myelinated Aδ- and unmyelinated C-fibers in patients with diabetic polyneuropathy and how they contribute to neuropathic pain.
Learn More >Adhesion-type GPCRs (aGPCRs) participate in a vast range of physiological processes. Their frequent association with mechanosensitive functions suggests that processing of mechanical stimuli may be a common feature of this receptor family. Previously, we reported that the aGPCR CIRL sensitizes sensory responses to gentle touch and sound by amplifying signal transduction in low-threshold mechanoreceptors (Scholz et al., 2017). Here, we show that is also expressed in high-threshold mechanical nociceptors where it adjusts nocifensive behaviour under physiological and pathological conditions. Optogenetic experiments indicate that CIRL lowers cAMP levels in both mechanosensory submodalities. However, contrasting its role in touch-sensitive neurons, CIRL dampens the response of nociceptors to mechanical stimulation. Consistent with this finding, rat nociceptors display decreased expression during allodynia. Thus, cAMP-downregulation by CIRL exerts opposing effects on low-threshold mechanosensors and high-threshold nociceptors. This intriguing bipolar action facilitates the separation of mechanosensory signals carrying different physiological information.
Learn More >The prevalence and burden of musculoskeletal (MSK) conditions are growing around the world, and low back pain (LBP) is the most significant of the five defined MSK disorders in the Global Burden of Disease (GBD) study. LBP has been the leading cause of non-fatal health loss for the last three decades. The objective of this study is to describe the current status and trends of the burden due to LBP in Brazil based on information drawn from the GBD 2017 study.
Learn More >Sex differences for chronic back pain (cBP) have been reported, with females usually exhibiting greater morbidity, severity and poorer response to treatment. Genetic factors acting in an age-specific manner have been implicated but never comprehensively explored. We performed sex- and age-stratified GWAS and SNP-by-sex interaction analysis for cBP defined as "Back pain for 3+ months" in 202,077 males and 237,754 females of European ancestry from UK Biobank. Two and seven non-overlapping genome-wide significant loci were identified for males and females, respectively. A male-specific locus on chromosome 10 near SPOCK2 gene was replicated in four independent cohorts. Four loci demonstrated SNP-by-sex interaction, although none of them were formally replicated. SNP-explained heritability was higher in females (0.079 vs 0.067, p = 0.006). There was a high, although not complete, genetic correlation between the sexes (r = 0.838±0.041, different from 1 with p = 7.8E-05). Genetic correlation between the sexes for cBP decreased with age (0.858±0.049 in younger people vs 0.544±0.157 in older people; p = 4.3E-05). There was a stronger genetic correlation of cBP with self-reported diagnosis of intervertebral disc degeneration in males than in females (0.889 vs 0.638; p = 3.7E-06). Thus, the genetic component of cBP in the UK Biobank exhibits a mild sex- and age-dependency. This provides an insight into the possible causes of sex- and age-specificity in epidemiology and pathophysiology of cBP and chronic pain at other anatomical sites.
Learn More >Little is known about risk factors for emergency department (ED) attendance for chronic pain (CP) management and the relative service burden. We examined emergency department (ED) utilisation in patients with chronic pain (CP), identified risk factors associated with attendance for chronic musculoskeletal pain (CMP) and estimated the comparative cost of treatment. The study cohort comprised a random sample of 3,700 adults from the general population in Tayside, Scotland. Linked regional extracts, spanning a 12-month period, were obtained from national registers, providing information on ED attendances, community-dispensed prescribing and outpatient clinic attendances. The NHS Scotland Cost Book was used to ascertain the current average cost of an ED attendance (£130; ∼$167).All-cause ED attendance was higher in those with CP (68.5%; n=252) than without (29.3%; n=967). In the entire cohort, more patients attended the ED for the treatment of CMP than for any other medical condition (n=119; 32.3% of those with CP). Risk factors for ED attendance for CMP were: recent analgesic dose decreases (OR=4.55); and transitioning from opioid to non-opioid analgesics (OR=5.08). Characteristics protective of ED attendance for CMP were: being in receipt of strong opioids (OR=0.21); transitioning from non-opioid to opioid analgesics (OR=0.25); recent analgesic dose increases (OR=0.24); and being prescribed tricyclic antidepressants (OR=0.10), benzodiazepines (OR=0.46) or hypnotics (OR=0.45). CMP was one of the most expensive conditions to treat (£17,680 (∼$22,668) per annum), conferring a substantial burden on ED services. Improved understanding of the risk/protective factors could inform healthcare redesign to reduce avoidable ED attendances for CMP management.
Learn More >The noradrenergic locus coeruleus nucleus is an important station in both the ascending and descending pain regulatory pathways. These neurons discharge in tonic and phasic modes in response to sensory stimuli. However, few studies have set out to characterize the electrophysiological response of the locus coeruleus to noxious stimuli in conditions of neuropathic pain. Thus, the effects of mechanical nociceptive stimulation of the sciatic nerve area on spontaneous (tonic) and sensory-evoked (phasic) locus coeruleus discharge were studied by extracellular recording in anesthetized rats seven, fourteen and twenty-eight days after chronic constriction injury. Minor significant electrophysiological changes were found seven and fourteen days after nerve injury. However, alterations to the spontaneous activity in both the ipsilateral and contralateral locus coeruleus were found twenty-eight days after nerve constriction, as witnessed by an increase of burst firing incidence and irregular firing patterns. Furthermore, noxious-evoked responses were exacerbated in the contralateral and ipsilateral nucleus at twenty-eight days after injury, as were the responses evoked when stimulating the uninjured paw. In addition, mechanical stimulation of the hindpaw produced a significant sensitization of neuronal tonic activity after 28 days of neuropathy. In summary, long-term nerve injury led to higher spontaneous activity and exacerbated noxious-evoked responses in the locus coeruleus to stimulation of nerve-injured and even uninjured hindpaws, coinciding temporally with the development of depressive and anxiogenic-like behavior.
Learn More >Early studies of deep brain stimulation (DBS) for various neurological disorders involved a temporary trial period where implanted electrodes were externalized, in which the electrical contacts exiting the patient's brain are connected to external stimulation equipment, so that stimulation efficacy could be determined before permanent implant. As the optimal brain target sites for various diseases (i.e., Parkinson's disease, essential tremor) became better established, such trial periods have fallen out of favor. However, deep brain stimulation trial periods are experiencing a modern resurgence for at least two reasons: (1) studies of newer indications such as depression or chronic pain aim to identify new targets and (2) a growing interest in adaptive DBS tools necessitates neurophysiological recordings, which are often done in the peri-surgical period. In this review, we consider the possible approaches, benefits, and risks of such inpatient trial periods with a specific focus on developing new DBS therapies for chronic pain.
Learn More >Previous studies suggest that immigration may influence the experience of pain.
Learn More >Today immersive environments such as Virtual Reality (VR) offer new opportunities for serious gaming in exercise therapy and psychoeducation. Chronic back pain (CBP) patients could benefit from exergames in VR. The requirements in older CBP patients for a VR pain therapy have not yet been determined in studies. The aim of the study was to perform a requirements analysis for the user group of geriatric patients with CBP for a VR exergame. The objective was to find out the expectations, desires, preferences and barriers in order to collect them as requirements for this vulnerable group and to determine frameworks of therapy by physiotherapists and psychotherapists.
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