Pain

Opioids are widely prescribed for chronic pain, including neuropathic pain despite growing evidence of long-term harm. Previous preclinical studies have documented exacerbation of nociceptive hypersensitivity, including that induced by peripheral nerve injury, by morphine. The present series of behavioral studies sought to replicate and extend our prior research, which demonstrated a multi-month exacerbation of nociceptive hypersensitivity by a 5-day course of morphine initiated 10 days after nerve injury. The current studies demonstrate that enduring exacerbation of nociceptive hypersensitivity is not restricted to morphine, but rather is also created by the clinically relevant opioids fentanyl and oxycodone when these are likewise-administered for 5 days beginning 10 days after nerve injury...

In this randomized clinical trial, we examined whether the effect of true acupuncture can be differentiated from sham acupuncture (pain and functionality) by analyzing quantitative sensory testing (QST) profiles in chronic pain participants. We recruited 254 healthy or chronic back and neck pain participants. Healthy subjects were included to control for a possible effect of acupuncture on baseline QST changes. Study participants received six sessions (twice weekly) of true acupuncture, sham acupuncture, or no acupuncture treatment (routine care)...

No abstract text is available yet for this article.

A recently defined structure, the rostromedial tegmental nucleus (RMTg; aka tail of the ventral tegmental area), has been proposed as an inhibitory control center for dopaminergic activity of the ventral tegmental area (VTA). This region is composed of GABAergic cells which send afferent projections to the ventral midbrain and synapse onto dopaminergic cells in the VTA and substantia nigra. These cells exhibit µ-opioid receptor immunoreactivity, and in-vivo, ex-vivo, and optogenetic/electrophysiological approaches demonstrate that morphine excites dopamine neurons by targeting receptors on GABAergic neurons localized in the RMTg...

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder resulting from germline mutations in the NF1 gene, which encodes neurofibromin. Patients experience a variety of symptoms, but pain in the context of NF1 remains largely under-recognized. Here, we characterize nociceptive signaling and pain behaviors in a miniswine harboring a disruptive NF1 mutation (exon 42 deletion). We present the first characterization of pain-related behaviors in a pig model of NF1, identifying unchanged agitation scores, lower tactile thresholds (allodynia), and decreased response latencies to thermal laser stimulation (hyperalgesia) in NF1 (females only) pigs...

No abstract text is available yet for this article.

Supportive touch has remarkable benefits in childbirth and during painful medical procedures. But does social touch influence pain neurophysiology, ie, the brain processes linked to nociception and primary pain experience? What other brain processes beyond primary pain systems mediate their analgesic effects? In this study, women (N = 30) experienced thermal pain while holding their romantic partner's hand or an inert device. Social touch reduced pain and attenuated functional magnetic resonance imaging activity in the Neurologic Pain Signature (NPS)-a multivariate brain pattern sensitive and specific to somatic pain-and increased connectivity between the NPS and both somatosensory and "default mode" regions...

Fibromyalgia (FM) is a prevalent syndrome, characterised by chronic widespread pain, fatigue and impaired sleep, that is challenging to diagnose and difficult to treat. The microbiomes of 77 women with FM and that of 79 control participants were compared using 16S rRNA gene amplification and whole genome sequencing. When comparing FM patients to unrelated controls using differential abundance analysis, significant differences were revealed in several bacterial taxa. Variance in the composition of the microbiomes was explained by FM-related variables more than by any other innate or environmental variable and correlated with clinical indices of FM...

Chronic pain is an unmet clinical problem with vast individual, societal and economic impact. Pathologic activity of the peripheral somatosensory afferents is one of the major drivers of chronic pain. This overexcitable state of somatosensory neurons is, in part, produced by the dysregulation of genes controlling neuronal excitability. Despite intense research, a unifying theory behind neuropathic remodelling is lacking. Here we show that transcriptional suppressor, repressor element 1-silencing transcription factor (REST, NRSF), is necessary and sufficient for the development of hyperalgesic state following chronic nerve injury or inflammation...

In previous studies that examined the impact of attention biases (ABs) on later pain outcomes, reaction times (RTs) in response to brief stimulus presentations had been used as measures of attention. Consequently, little is known about effects of ABs assessed during presentations of cues or biases in prolonged attention towards pain stimuli as influences on subsequent functioning. To address these gaps, 89 adults with chronic pain (68 women, 21 men) engaged in a baseline dot-probe task in which visual attention was tracked during injury-neutral (I-N) image pair presentations as well as a 6-month follow-up reassessing pain intensity and interference from pain...

We conducted a randomized controlled trial of an individually-tailored, virtual perspective-taking intervention to reduce race and socioeconomic (SES) disparities in providers' pain treatment decisions. Physician residents and fellows (n=436) were recruited from across the United States for this two-part online study. Providers first completed a bias assessment task in which they made treatment decisions for virtual patients with chronic pain who varied by race (Black/White) and SES (low/high). Providers who demonstrated a treatment bias were randomized to the intervention or control group...

Preclinical studies suggest that type 2 hyperpolarization-activated cyclic nucleotide gated ion channels (HCN2) are necessary for neuropathic pain. This trial assessed the influence of ivabradine, a non-selective HCN channel blocker, on capsaicin-induced hyperalgesia and pain in healthy human subjects. An enriched population comprising subjects who developed >20cm2 of punctate hyperalgesia from topical capsaicin (0.5% cream applied onto 9cm2 area) was identified. These subjects then received ivabradine (15mg) or placebo one hour prior to capsaicin application in randomly allocated order in a crossover study...

Three clinical scales (the Nociception-Coma-Scale adapted for Intubated-patients (NCS-I), its Revised version (NCS-R-I), and the Behavioral-Pain-Scale (BPS)) and videopupillometry were compared for measuring pain in intubated, non-communicating, critically ill, brain-injured (CIBI) patients. Pain assessment was performed before, during, just after and 5-min after three procedures: the reference non-nociceptive procedure (assessment of the Richmond-Agitation-Sedation-Scale), and two nociceptive procedures (turning and tracheal-suctioning)...

Emerging evidence suggests that MSK should be viewed from a biopsychosocial perspective and consider the influence of family factors. We conducted a review with meta-analysis to provide summary estimates of effect of family history of pain on childhood MSK pain, and explore whether specific family pain factors influence the strength of the association (PROSPERO CRD42018090130). Included studies reported associations between family history of pain and non-specific MSK pain in children (age <19 years). The outcome of interest was MSK pain in children...

Opioid use and sleep disruption are prevalent in fibromyalgia. Yet, the effects of opioids on physiological sleep in fibromyalgia are unclear. This study assessed associations between opioid use/dosage and polysomnographically assessed sleep in patients with fibromyalgia and insomnia (FMI) and examined moderating effects of age and pain. Participants (N = 193, Mage = 51.7, SD = 11.8, range = 18-77) with FMI completed ambulatory polysomnography and 14 daily diaries. Multiple regression determined whether commonly prescribed oral opioid use or dosage (among users) independently predicted or interacted with age/pain intensity to predict sleep, controlling for sleep medication use and apnea hypopnea index...

Mounting evidence suggests that the spinal dorsal horn (SDH) contains multiple subpopulations of inhibitory interneurons that play distinct roles in somatosensory processing, as exemplified by the importance of spinal dynorphin-expressing neurons for the suppression of mechanical pain and chemical itch. While it is clear that GABAergic transmission in the SDH undergoes significant alterations during early postnatal development, little is known about the maturation of discrete inhibitory "microcircuits" within the region...

The incidence of persistent opioid use after lung surgery is high. Although adverse effects by opioids have been well described, it is unknown whether persistent opioid use is associated with worse survival.Patients who received a lobectomy for stage I NSCLC from 2007 - 2013 were identified from the SEER-Medicare database. Opioid use was ascertained through records of prescriptions filled through Part D. Patients were matched 2:1 according to their likelihood of persistent opioid use, which was defined as any opioid prescription filled 3-6 months after surgery...

The prevalence of obesity has grown rapidly over the past several decades and has been accompanied by an increase in the prevalence of chronic pain and prescription opioid use. Obesity, through its association with pain, may represent an important contributor to the opioid epidemic. This cross-sectional study investigated the relationship between obesity and prescription opioid use among adults aged 35-79 using data from the National Health and Nutrition Examination Survey (NHANES, 2003-2016). Relative to normal weight, BMIs in the overweight (OR, 1...

No abstract text is available yet for this article.

Wide dynamic range (WDR) neurons of the spinal dorsal horn respond to a wide range of innocuous and noxious mechanical stimulation and encode the intensity of mechanical stimuli as changes in firing rate. However, there are inconsistent findings regarding whether WDR neuron stimulus encoding activity is altered in pathological pain states. This inconsistency may arise from differences in the pain models used or in the experimental conditions themselves. In the present study, we use a meta-regression approach to examine which variables modulate and determine WDR activity...