Pain

Chemotherapy-induced neuropathic pain (CINP) in both sexes compromises many current chemotherapeutics and lacks a FDA-approved therapy. We recently identified the sphingosine-1-phosphate receptor subtype 1 (S1PR1) and A3 adenosine receptor subtype (A3AR) as novel targets for therapeutic intervention. Our work in male rodents using paclitaxel, oxaliplatin and bortezomib showed robust inhibition of CINP with either S1PR1 antagonists or A3AR agonists. The S1PR1 functional antagonist FTY720 (Gilenya®) is FDA approved for treating multiple sclerosis and selective A3AR agonists are in advanced clinical trials for cancer and inflammatory disorders, underscoring the need for their expedited trials in CINP patients as chemotherapy adjuncts...

No abstract text is available yet for this article.

The bladder is innervated by primary afferent nerve fibres that detect bladder distension and, via projections into the spinal cord, provide sensory input to the central nervous system circuits regulating bladder sensation and function. Uropathogenic E. coli (UPEC) are the primary cause of urinary tract infection (UTI) in adults, inducing clinical symptoms characterised by exaggerated bladder sensation, including urgency, frequency, and pelvic pain. However, the mechanisms underlying UTI-induced modulation of bladder afferent function have yet to be explored...

Chronic back pain is a major global health problem, while its treatment is hampered by a lack of efficacy and restricted safety profile of common front-line therapies. The present trial aims to determine whether a 3-week open-label placebo treatment reduces pain intensity, and subjective and objective functional disability in chronic back pain patients. This randomized controlled trial, following a pretest-posttest design, enrolled 127 chronic back pain patients (pain duration > 12 weeks) from the Back Pain Center, Neurology, University Hospital Essen, Germany...

Rescue medication is commonly offered to participants in placebo-controlled trials of analgesic drugs. The use of pain medication in addition to the placebo or experimental drug may complicate the interpretation of effects and tolerability, but this issue has received little methodological attention. This study examined the handling and reporting of rescue and concomitant analgesic use in trials of pharmacotherapy for neuropathic pain and low back pain. We based our review on 265 trials included in two recent systematic reviews, 83 trials of low back pain and 182 of neuropathic pain...

Dissecting the organization of circuit pathways involved in pain affect is pivotal for understanding behavior associated with noxious sensory inputs. The central nucleus of amygdala (CeA) is comprised of distinct populations of inhibitory GABAergic neurons expressing a wide range of molecular markers. CeA circuits are associated with aversive learning and nociceptive responses. The CeA receives nociceptive signals directly from the parabrachial nuclei (PBn), contributing to the affective and emotional aspects of pain...

Early detection of patients with chronic diseases at risk of developing persistent pain is clinically desirable for timely initiation of multimodal therapies. Quality follow-up registries may provide the necessary clinical data; however, their design is not focused on a specific research aim, which poses challenges on the data-analysis strategy. Here, machine-learning was used to identify early parameters that provide information about a future development of persistent pain in rheumatoid arthritis (RA). Data of 288 patients were queried from a registry based on the Swedish Epidemiological Investigation of RA (EIRA)...

Brain derived neurotrophic factor (BDNF) and the high affinity receptor tropomyosin receptor kinase B (TrkB) have important roles in neuronal survival and in spinal sensitization mechanisms associated with chronic pain. Recent clinical evidence also supports a peripheral role of BDNF in osteoarthritis (OA), with synovial expression of TrkB associated with higher OA pain. The aim of this study was to use clinical samples and animal models to explore the potential contribution of knee joint BDNF / TrkB signalling to chronic OA pain...

The aims of this study review were to: systematically identify the current evidence base of randomised controlled trials (RCTs) of spinal cord stimulation (SCS) placebo (or 'sham') trials for neuropathic pain and (2) to undertake a meta-analysis to investigate the effectiveness of SCS when compared with a placebo comparator arm. Electronic databases were searched from inception until January 2019 for RCTs of SCS using a placebo/sham control. Searches identified eight eligible placebo-controlled randomised trials of SCS for neuropathic pain...

In 2014, the PACE trial demonstrated that paracetamol had no effect compared to placebo in acute low back pain (LBP). However, non-compliance was a potential limitation of this trial. The aim of this study was to investigate the efficacy of paracetamol in acute low back pain among compliers.Using individual participant data from the PACE trial (ACTN12609000966291), Complier Average Causal Effects (CACE), Intention-to-treat (ITT) and Per Protocol (PP) estimates were calculated for pain intensity (primary), and disability, global rating of symptom change and function (all secondary) after two weeks of follow-up...

Emerging evidence has indicated that colony-stimulating factor-1 (CSF1) modulates neuroinflammation in the central nervous system (CNS) and the development of neuropathic pain, while the underlying mechanism remains unknown. Here, we identified the increased expression of CSF1 derived from activated astrocytes in the ipsilateral dorsal horn in rats with spinal nerve ligation (SNL). Suppression of CSF1 expression alleviated neuroinflammation, neuronal hyperexcitability and glutamatergic receptor subunit upregulation in the dorsal horn and improved SNL-induced pain behavior...

The investigation of neurotransmitter systems in placebo and nocebo effects has improved our understanding of these phenomena. Yet, the majority of studies involve healthy participants. As the pain modulatory system may differ in healthy participants and patients with chronic pain, it is important to investigate the evidence for neurotransmitter involvement in placebo and nocebo effects in each of these populations. PubMed, Embase, Scopus databases, and the Cochrane Library were searched for articles investigating the endogenous opioid, endocannabinoid, dopaminergic, oxytocinergic, vasopressinergic, and cholecystokinergic (CCKergic) systems in placebo and nocebo effects in pain...

Opioids are the most powerful analgesics available to date. However, they may also induce adverse effects including paradoxical opioid-induced hyperalgesia (OIH). A mechanism that might underlie OIH is the amplification of synaptic strength at spinal C-fibre synapses after withdrawal from systemic opioids such as remifentanil ("opioid-withdrawal-LTP").Here, we show that both, the induction as well as the maintenance of opioid-withdrawal-LTP were abolished by pharmacological blockade of spinal glial cells...

No abstract text is available yet for this article.

Spinal hyperexcitability is a key event in the development of persistent pain, and arises partly from alterations in the number and localization of AMPA-type glutamate receptors. However, determining precisely where these changes occur is challenging due to the requirement for multiplex labelling and nanoscale resolution. The recent development of super-resolution light microscopy provides new tools to address these challenges. Here, we apply combined confocal/direct STochastic Optical Reconstruction Microscopy (dSTORM) to reveal changes in calcium-permeable subunits of AMPA-type glutamate receptors (GluA1) at identified SCDH primary afferent terminals in a model of inflammatory pain...

Endogenous opioid peptides and exogenous opioids modulate immune function and animal and human studies have shown that some have a depressant immunomodulatory effect. This is potentially of high clinical significance for example in cancer patients and surgery.The primary objective of this pilot study was to evaluate the effect of morphine and oxycodone on immune pathways associated with immunosuppression in gynecological laparotomy patients.Gene expression was analyzed in CD4+, CD8+ and NK cells using the 3' Affymetrix microarray...

Human cold perception and nociception play an important role in persisting pain. However, species differences in the target temperature of thermosensitive ion channels expressed in peripheral nerve endings have fueled discussions about the mechanism of cold nociception in humans. Most frequently implicated thermosensors are members of the transient receptor potential (TRP) ion channel family TRPM8 and TRPA1. Regularly observed, distinct cold pain phenotype groups suggested the existence of interindividually differing molecular bases...

Low back pain (LBP) has been inconsistently associated with enhanced pro-nociceptive and impaired anti-nociceptive mechanisms. It remains unknown whether alterations are causal, consequential or coincidental to pain presence. This study investigated pro-nociceptive and anti-nociceptive mechanisms in recurrent LBP (RLBP) patients across painful and pain-free periods, compared to age/gender-matched asymptomatic controls. During a painful episode (Day0) and when pain-free (Day28) thirty RLBP patients were assessed and compared to thirty controls over the same timeframe...

No abstract text is available yet for this article.

Pain catastrophizing has been shown to predict greater pain and less physical function in daily life for chronic pain sufferers, but its effects on close social partners have received much less attention. The overall purpose of the present study was to examine the extent to which pain catastrophizing is an interpersonal coping strategy that is maladaptive for patients and their spouses. A total of 144 older knee osteoarthritis patients and their spouses completed baseline interviews and a 22-day diary assessment...