Pain

Diffuse noxious inhibitory controls (DNIC) is a pain inhibits pain phenomenon demonstrated in humans and animals. DNIC is diminished in many chronic pain states, including neuropathic pain. The efficiency of DNIC has been suggested to prospectively predict both the likelihood of pain chronification and treatment response. Little is known as to why DNIC is dysfunctional in neuropathic pain. Here, we evaluated DNIC in the rat L5/L6 spinal nerve ligation (SNL) model of chronic pain using both behavioral and electrophysiological outcomes...

Postoperative pain management continues to be suboptimal due to the lack of effective non-opioid therapies and absence of understanding of sex-driven differences. Here we asked how the NLRP3 inflammasome contributes to postoperative pain. Inflammasomes are mediators of the innate immune system that are responsible for activation and secretion of IL-1β upon stimulation by specific molecular signals. Peripheral IL-1β is known to contribute to the mechanical sensitization induced by surgical incision. However, it is not known which inflammasome mediates the IL-1β release following surgical incision...

Peripheral inflammation produces a long-lasting latent sensitization of spinal nociceptive neurons that is masked by tonic inhibitory controls. We explored mechanisms of latent sensitization with an established four-step approach: 1) induction of inflammation; 2) allow pain hypersensitivity to resolve; 3) interrogate latent sensitization with a channel blocker, mutant mouse, or receptor antagonist; 4) disrupt compensatory inhibition with a receptor antagonist so as to reinstate pain hypersensitivity. We found that the neuropeptide Y Y1 receptor antagonist BIBO3304 reinstated pain hypersensitivity, indicative of an unmasking of latent sensitization...

Therapeutic interventions for neuropathic pain (NP), such as the NMDA-antagonist ketamine, can vary widely in effectiveness; Here, we conducted a longitudinal functional MRI study to test the hypothesis that the pain relieving effect of ketamine is due to reversal of abnormalities in regional low frequency brain oscillations (LFOs) and abnormal cross-network functional connectivity (FC) of the dynamic pain connectome. We found that: 1) ketamine decreased regional LFOs in the posterior cingulate cortex (PCC) of the default mode network (DMN), 2) a machine learning algorithm demonstrated that treatment-induced brain changes could be used to make generalizable inferences about pain relief, 3) treatment responders exhibited a significant decrease in cross-network static FC between the PCC and regions of the sensorimotor (SM) and salience networks following treatment, 4) the degree of reduced cross-network FC was correlated with the amount of pain relief, and 5) ketamine treatment did not produce significant differences in static or dynamic FC within the ascending nociceptive- or descending antinociceptive pathway...

Chronic pain affects 1 in 5 people and has been shown to disrupt attention. Here, we investigated whether pain disrupts everyday decision making. In Study 1, 1322 participants completed two tasks online: a shopping decisions task and a measure of decision outcomes over the previous 10 years. Participants who were in pain during the study made more errors on the shopping task than those who were pain-free. Participants with a recurrent pain condition reported more negative outcomes from their past decisions than those without recurrent pain...

Based on previous clinic-based MRI studies showing regional differences in the cerebral cortex between those with and without headache, we hypothesized that headache sufferers have a decrease in volume, thickness or surface area in anterior cingulate cortex (ACC), prefrontal cortex (PFC), and insula. In addition, exploratory analyses on volume, thickness and surface area across the cerebral cortical mantle were performed. 1006 participants (50-66 years) from the general population were selected to an imaging study of the head at 1...

Post-traumatic injury pain is commonly treated with oral nonsteroidal anti-inflammatory drugs (NSAIDs). However, oral NSAIDs causes several adverse events, with topical formulations arising as an important alternative. Therefore, we aimed to evaluate the efficacy and safety of loxoprofen patch in the treatment of patients with post-traumatic pain. This phase III, randomized, double-blind, non-inferiority study enrolled Brazilian patients aged 18-65 years diagnosed with lower and upper limbs post-traumatic injury who were experiencing moderate or severe pain...

While several studies have found that chronic pain is characterized by increased cross-network connectivity between salience, sensorimotor, and default mode (DMN) networks, a large sample-size investigation allowing a more reliable evaluation of somatotopic specificity and subgroup analyses with linkage to clinical pain intensity has been lacking. We enrolled healthy adults and a large cohort of patients (N=181) suffering from chronic low back pain (cLBP). To specifically link brain connectivity with clinical pain intensity, patients were scanned at baseline and after performing physical maneuvers that exacerbated pain...

Clinicians report reluctance to deliver opioid-tapering advice to patients with chronic pain, in part due to concerns that patients will be angry and dissatisfied. An experiment was conducted to examine chronic pain patients' emotional and attitudinal responses to simulated opioid-tapering advice. Patients scheduled for an initial assessment at a tertiary pain clinic and currently taking opioid medications for pain (N = 196) were randomly assigned to view video footage of a standardized patient receiving one of three forms of treatment advice: 1) stay on current medication, 2) change to a different pain medication, or 3) taper off pain medications and participate in a CBT-based pain self-management program...

Chronic or persistent pain is a growing global health problem. Effective management of pain emerging in childhood may prevent long-term health and vocational consequences. Internationally, paediatric pain services are a limited resource and, as such, must strive to improve equity, outcomes and value for money. The Paediatric electronic Persistent Pain Outcomes Collaboration (PaedePPOC) is a bi-national paediatric outcome measurement centre that aims to measure, benchmark, and improve children's specialist pain services in Australasia...

Pain after surgery remains a major health problem, calling for optimized treatment regimens to maximize the efficacy of pharmacological interventions. In this randomized controlled trial, we tested in a routine surgical treatment setting whether postoperative pain can be reduced by a brief preoperative intervention, i.e., positive verbal suggestions in combination with sham acupuncture, designed to optimize treatment expectations. We hypothesized that the expectancy intervention as add-on to patient-controlled intravenous analgesia (PCIA) with morphine reduces patient-reported postoperative pain and improves satisfaction with analgesia...

Chemotherapy-induced peripheral neuropathy (CIPN) is a severe adverse effect that occurs secondary to anticancer treatments and has no known preventive or therapeutic strategy. Therapeutic hypothermia has been shown to be effective in protecting against central and peripheral nervous system injuries. However, the effects of therapeutic hypothermia on CIPN have rarely been explored. We induced lower back hypothermia (LBH) in an established paclitaxel-induced CIPN rat model and found that the paclitaxel-induced impairments observed in behavioral, electrophysiological, and histological impairments were inhibited by LBH when applied at an optimal setting of 24°C to the sciatic nerve and initiated 90 min before paclitaxel infusion...

Rare pain-insensitive individuals offer unique insights into how pain circuits function and have led to the development of new strategies for pain control. We investigated pain sensitivity in humans with WAGR (Wilms tumor, aniridia, genitourinary anomaly, and range of intellectual disabilities) syndrome, who have variably sized heterozygous deletion of the 11p13 region. The deletion region can be inclusive or exclusive of the brain-derived neurotrophic factor (BDNF) gene, a crucial trophic factor for nociceptive afferents...

No abstract text is available yet for this article.

Multimodal neuroimaging studies provide support for a role of alterations in sensory processing circuits and endogenous pain modulatory systems in provoked vestibulodynia (PVD). In this study we tested the hypotheses that PVD compared to healthy controls (HCs) would demonstrate gray matter volume (GMV) alterations in regions associated with sensorimotor, corticothalamic, and basal ganglia circuits. We also tested the replicability of previously reported gray matter increases in basal ganglia and hippocampal volumes in PVD versus HCs...

No abstract text is available yet for this article.

In this randomized, double-blind, placebo-controlled crossover study, we investigated if a peripheral nerve block could temporarily eliminate phantom and stump pain after amputation. Amputees with constant postamputation pain were included and randomized to receive a nerve block with lidocaine 2% with adrenaline or saline in a crossover design. Spontaneous phantom and stump pain and evoked responses were assessed at baseline and at fixed time points until 120 minutes after lidocaine or saline injection. The primary outcome was the difference in absolute change between worst pain intensity, either phantom or stump pain, at baseline and at 30 minutes after lidocaine or saline injection...

No abstract text is available yet for this article.

Previous studies have shown a robust correlation between variability of clinical pain scores and responsiveness to placebo (but not active drug) in pain studies, but explanations for these relationships are lacking. We investigated this further by assessing relationship between the Focused Analgesia Selection Test (FAST); a psychophysical method that quantifies pain reporting variability in response to experimental stimuli, variability of daily clinical pain scores as captured via diary, and response to treatment in the context of a randomized controlled crossover trial of naproxen vs...

The nucleus accumbens (NAc) has been implicated in sleep, reward, and pain modulation, but the relationship between these functional roles is unclear. This study aimed to determine if NAc function at the onset and offset of a noxious thermal stimulus is enhanced by rewarding music, and if that effect is reversed by experimental sleep disruption. Twenty-one healthy subjects underwent functional MRI (fMRI) scans on two separate days following both uninterrupted sleep and experimental sleep disruption. During fMRI scans, participants experienced noxious stimulation while listening to individualized rewarding or neutral music...