Pain

Propranolol is a non-selective beta-adrenergic receptor antagonist. A multicenter, randomized, double-blind, placebo-controlled, parallel-group, phase 2b trial enrolled participants aged 18-65 years with temporomandibular disorder (TMD) myalgia to evaluate efficacy and safety of propranolol compared with placebo in reducing facial pain. Participants were randomized 1:1 to either extended-release propranolol hydrochloride (60 mg, BID) or placebo. The primary endpoint was change in facial pain index (FPI = facial pain intensity multiplied by facial pain duration, divided by 100)...

The inflammatory/immune response at the site of peripheral nerve injury participates in the pathophysiology of neuropathic pain. Nevertheless, little is known about the local regulatory mechanisms underlying peripheral nerve injury that counteract the development of pain. Here, we investigated the contribution of regulatory T (Treg) cells to the development of neuropathic pain by using a partial sciatic nerve ligation model (PSNL) in mice. We showed that Treg cells infiltrate and proliferate in the site of peripheral nerve injury...

Cognitive impairment is one of the most common complications associated with chronic pain. Almost 20% of chronic pain patients suffer from cognitive impairment, which may substantially influence their quality of life. Levels of major excitatory neurotransmitters in the central nervous system, and alterations in the glutamatergic system may influence cognitive function and the pain sensory pathway. In the present study, we adopted the spare nerve injury model to establish the progress of chronic pain and investigated the mechanism underlying the cognitive aspect related to it...

No abstract text is available yet for this article.

No large-cohort studies that examine racial effects on placebo hypoalgesic effects exist. To fill this void, we studied placebo effects in healthy and chronic pain participants self-identified as either African-American/Black (AA/Black) or White. We enrolled 372 study participants, 186 with a diagnosis of temporomandibular disorder (TMD) and 186 race, sex, and age matched healthy participants to participate in a placebo experiment. Using a well-established paradigm of classical conditioning with verbal suggestions, each individual pain sensitivity was measured to calibrate the temperatures for high- and low-pain stimuli in the conditioning protocol...

We investigated the contribution of nucleus locus ceruleus (LC) to the development of pain-associated affective behavior. Mice of both sexes were subjected to sciatic nerve cuffing, a model of peripheral nerve injury, and monitored for 45 days. While the thermal and mechanical thresholds were equally decreased in both males and females, only the male mice developed anxiodepressive-like behavior, which was complemented by suppressed hippocampal neurogenesis. Furthermore, the LC activity was lower in males when compared to females subjected to sciatic cuffing...

Fibromyalgia is a common and complex long-term pain condition. Despite advancements in our understanding and treatment of fibromyalgia, patients report patchy healthcare provision and frustrating journeys through the healthcare system. To inform how best to deliver care, we undertook two narrative reviews examining existing evidence on a) models of care for fibromyalgia and b) patients' experiences, preferences and unmet needs regarding their healthcare. Seven databases were systematically searched. Quantitative data was narratively synthesised and qualitative data thematically analysed...

Pain signals the presence of potential harm, captures attention, and can inhibit performance on concurrent tasks. What is less well known, however, is whether such attentional capture also occurs in a wider social context, such as when observing people in pain. In order to explore this possibility, we adopted a novel social-cue detection methodology: the bodies-in-the-crowd task. Two experiments are reported that consider whether nonverbal cues of pain, happiness and anger as expressed through body postures would capture and hold attention...

Dorsal root ganglion (DRG) neurons detect sensory inputs and are crucial for pain processing. They are often studied in vitro as dissociated cell cultures with the assumption that this reasonably represents in vivo conditions. However, to our knowledge, no study has directly compared genome-wide transcriptomes of DRG tissue in vivo versus in vitro, or between laboratories and culturing protocols. Comparing RNA sequencing-based transcriptomes of native to cultured (4 days in vitro) human or mouse DRG, we found that the overall expression levels of many ion channels and GPCRs specifically expressed in neurons are markedly lower although still expressed in culture...

Although a fluctuating pattern of orofacial pain across the life span has been proposed, data on its natural course is lacking. The longitudinal course of orofacial pain in the general population was evaluated using data from routine dental check-ups at all Public Dental Health services in Västerbotten, Sweden. In a large population sample, two screening questions were used to identify individuals with pain once a week or more in the orofacial area. Incidence and longitudinal course of orofacial pain were evaluated using annual data for 2010-2017...

Extracellular nucleosides and nucleotides have widespread functions in responding to physiological stress. The "purinome" encompasses four G protein-coupled receptors (GPCRs) for adenosine, eight GPCRs activated by nucleotides (P2YRs), seven adenosine 5'-triphosphate(ATP)-gated P2X ion channels, as well as the associated enzymes and transporters that regulate native agonist levels. Purinergic signaling modulators, such as receptor agonists and antagonists, have potential for treating chronic pain...

We aimed to evaluate the efficacy of an enhanced mindfulness based stress reduction (MBSR+) versus stress management for headache (SMH). We performed a randomized, assessor-blind, clinical trial of 98 adults with episodic migraine recruited at a single academic center comparing MBSR+ (n=50) to SMH (n=48). MBSR+ and SMH were delivered weekly by group for 8 weeks, then bi-weekly for another 8 weeks. The primary clinical outcome was reduction in headache days from baseline to 20 weeks. MRI outcomes included activity of left dorsolateral prefrontal cortex (DLPFC) and cognitive task network during cognitive challenge, resting state connectivity of right dorsal anterior insula (daINS) to DLPFC and cognitive task network, and gray matter volume of DLPFC, daINS, and anterior midcingulate...

Physical disuse could lead to a state of chronic pain typified by complex regional pain syndrome type I due to fear of pain through movement (kinesiophobia) or inappropriate resting procedures. However, the mechanisms by which physical disuse is associated with acute/chronic pain and other pathological signs remain unresolved. We have previously reported that inflammatory signs, contractures, disuse muscle atrophy, spontaneous pain-like behaviors, and chronic widespread mechanical hyperalgesia based on central plasticity occurred after 2-weeks of cast immobilization in chronic post-cast pain (CPCP) rat model...

Transcribed ultraconserved regions (T-UCRs) are a novel class of long noncoding RNAs (lncRNAs) and are completely conserved in humans, rats, and mice. T-UCRs have been implicated in diverse biological processes; however, very little is currently known about their role in pain modulation. Here, we found that the level of the spinal T-UCR uc.153 was significantly increased in a mouse model of sciatic nerve chronic constriction injury (CCI)-induced chronic neuropathic pain. The knockdown of spinal uc.153 prevented and reversed CCI-induced pain behaviours and spinal neuronal sensitization...

Some forms of chronic pain are thought to be driven and maintained by nociceptive input, which can drive plasticity within nociceptive pathways. We have previously identified abnormalities along the entire nociceptive pathway in chronic myalgic temporomandibular disorders (mTMD), including the trigeminal nerves, brainstem pathways, and in the thalamus and somatosensory cortex. These data suggest that there is a peripheral nociceptive drive in mTMD, but the source of this nociceptive activity remains unknown...

The endogenous opioidergic system is critically involved in the cognitive modulation of pain. Slow-breathing based techniques are widely utilized non-pharmacological approaches to reduce pain, although the active mechanisms of actions supporting these practices are poorly characterized. Growing evidence suggest that mindfulness-meditation, a slow-breathing technique practiced by non-reactively attending to breathing sensations, engages multiple unique neural mechanisms that bypass opioidergically mediated descending pathways to reduce pain...

Women who develop bladder pain syndrome (BPS), irritable bowel syndrome, or dyspareunia frequently have an antecedent history of dysmenorrhea. Despite the high prevalence of menstrual pain, its role in chronic pelvic pain emergence remains understudied. We systematically characterized bladder, body, and vaginal mechanical sensitivity with quantitative sensory testing in women with dysmenorrhea (DYS, n = 147), healthy controls (HCs) (n = 37), and women with BPS (n = 25). Previously, we have shown that a noninvasive, bladder-filling task identified a subset of women with both dysmenorrhea and silent bladder pain hypersensitivity, and we repeated this to subtype dysmenorrhea sufferers in this study (DYSB; n = 49)...

Distinct pain experiences are shaped both by personal attributes and characteristics of noxious stimuli. An individual's capacity for endogenous pain inhibition (reflected by conditioned pain modulation (CPM)), their resilience, and the pain unpleasantness and salience of painful stimuli can impact their pain perception. Here, we aimed to determine how individual variability in CPM relates to sex and resilience as personal attributes, and pain unpleasantness and salience of the CPM conditioning stimulus (CS)...

Nocebo hyperalgesia is a clinically relevant phenomenon and may be formed as a result of associative learning, implemented by classical conditioning. This study explored for the first time distinct nocebo conditioning methods and their consequences for nocebo attenuation methods. Healthy participants (N = 140) were recruited and randomized to the following nocebo hyperalgesia induction groups: conditioning with continuous reinforcement (CRF), conditioning with partial reinforcement (PRF), and a sham-conditioning control group...

No abstract text is available yet for this article.