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To conduct a systematic literature review of peripheral nerve stimulation (PNS) for pain.
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. Here, our aim was to determine whether structural abnormalities exist in the muscles of mastication of patients with chronic mTMD. Specifically, we tested whether the volume of the temporalis muscle and its tendon-aponeurosis complex (TAC, a structure that dissipates forces in a muscle) in mTMD patients differ compared to age- and sex-matched controls. To do so, we segmented these structures on T1-weighted structural magnetic resonance images. We found that muscle volumes in mTMD were not different to controls. However, the mTMD group had significantly smaller volumes of the bilateral temporalis TAC, and thus a smaller TAC-to-muscle volume ratio. These findings were consistent across 2 independent cohorts of 17 mTMD patients, compared to 17 age- and sex-matched controls. We propose a model where reduced TAC-to-muscle ratio could result in a predisposition to muscle tissue injury. In sum, abnormalities of the temporalis muscles in mTMD supports our hypothesis that chronic mTMD pathophysiology may be related to peripheral nociceptive barrage originating from the muscles of mastication.
Chronic pain and subfertility are the main symptoms of concern in women with endometriosis. In order to find new therapeutic options to suppress the pain, translational animal models are indispensable. We have developed a new automated, experimental setup, with full consideration for animal wellbeing, to determine whether operant behaviour can reveal abdominal hyperalgesia in rats with surgically-induced endometriosis, in order to assess whether abdominal hyperalgesia affect behavioural parameters. Endometriosis was induced by transplantation of uterine fragments in the abdominal cavity. Control groups consisted of sham-operated rats and non-operated rats. We have developed an operant chamber (Skinnerbox) which includes a barrier. The rat can climb the barrier in order to reach the food pellet, increasing in this way the pressure to the abdomen. We show that endometriosis rats collect significantly less sugar pellets when compared with the control rats after the introduction of the barrier. In the Skinnerbox experiment, we showed that in a positive operant setting, the introduction of a barrier results in a contrast of operant behaviour of endometriosis rats and control groups, perchance as a result of abdominal discomfort/hyperalgesia due to surgically-induced endometriosis. This is a promising start for the further development of a refined animal model to monitor abdominal discomfort/hyperalgesia in rats with surgically-induced endometriosis.
Chronic pain presents a huge burden for individuals and society and evidence suggests intrinsic links with loneliness, social exclusion and sleep. Research examining how these factors interact is warranted. We aimed to explore the relationships between social exclusion, loneliness, acute and chronic pain, and the influence of poor sleep, in the general UK population. A cross-sectional analysis of UKBiobank participants with baseline data for acute and chronic pain, loneliness and sleep. Principal components analysis (PCA) used data relating to social isolation and deprivation to establish a composite measure of social exclusion. Binary logistic regression analyses were performed. 502,528 UKBiobank participants (mean age = 56.6years, 54.4%female, 94.6%white) were included in the analysis. PCA suggested three social exclusion factors "social participation", "individual deprivation" and "area deprivation". Loneliness significantly predicted acute (OR:1.887; 95%CI1.857-1.917) and chronic pain (OR:1.843; 95%CI1.816-1.870). Each social exclusion factor alone and in combination significantly predicted pain with largest effects for individuals scoring high on all social exclusion factors, for acute (OR:2.087; 95%CI2.026-2.150) and chronic (OR:2.314; 95%CI2.249-2.380) pain. Coefficients remained statistically significant when models were adjusted for demographics and sleep. Social exclusion (as a multifaceted construct) and loneliness are associated with an increased prevalence of acute and chronic pain. Poor sleep has a potential mediating effect on these associations. Exploration of the incidence of pain in loneliness and social exclusion in the general population is warranted. From a public health perspective these findings could be used to design social interventions to prevent or manage pain and mitigate social exclusion.
Although a fluctuating pattern of orofacial pain across the life span has been proposed, data on its natural course are 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, 2 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 to 2017. To evaluate predictors for orofacial pain remaining over time, individuals who reported pain on at least 2 consecutive dental check-ups were considered persistent. A generalized estimating equation model was used to analyze the prevalence, accounting for repeated observations on the same individuals. In total, 180,308 individuals (equal gender distribution) were examined in 525,707 dental check-ups. More women than men reported orofacial pain (odds ratio 2.58, 95% confidence interval [CI] 2.48-2.68), and there was a significant increase in the prevalence of reported pain from 2010 to 2017 in both women and men. Longitudinal data for 135,800 individuals were available for incidence analysis. Women were at higher risk of both developing orofacial pain (incidence rate ratio 2.37; 95% CI 2.25-2.50) and reporting pain in consecutive check-ups (incidence rate ratio 2.56; 95% CI 2.29-2.87). In the northern Swedish population studied, the prevalence of orofacial pain increases over time and more so in women, thus indicating increasing differences in gender for orofacial pain.
Chemotherapies of varying classes often cause neuropathy and debilitating chemotherapy-induced neuropathic pain sufficient to limit treatment and reduce quality of life for many patients battling cancer. There are currently no effective preventive or alleviative treatments for chemotherapy-induced neuropathic pain. Preclinical models have been developed to test candidate chemotherapy-induced neuropathic pain treatments; however, studies using these models rarely provide direct comparisons of effects of different chemotherapies or assess the degree to which chemotherapies produce clinically relevant signs of pain-depressed behavior. Male and female Sprague-Dawley rats received four injections of vehicle, paclitaxel, oxaliplatin, vincristine, or bortezomib on alternate days. Mechanical hypersensitivity, body weight, and food-maintained operant responding were evaluated before, during, and for up to 42 days after initiation of treatment. Morphine potency and effectiveness to reverse chemotherapy-induced effects were also evaluated. All four chemotherapies produced dose-dependent and sustained mechanical hypersensitivity in all rats. Vincristine and oxaliplatin produced transient weight loss and decreases in food-maintained operant responding in all rats, whereas paclitaxel and bortezomib produced lesser or no effect. At 4 weeks after treatment, operant responding was depressed only in paclitaxel-treated males. Morphine reversed mechanical hypersensitivity in all rats but failed to reverse paclitaxel-induced depression of operant responding in males. We conclude that chemotherapy treatments sufficient to produce sustained mechanical hypersensitivity failed to produce sustained or morphine-reversible behavioral depression in rats. Insofar as pain-related behavioral depression is a cardinal sign of chemotherapy-induced neuropathic pain in humans, these results challenge the presumption that these chemotherapy-dosing regimens are sufficient to model clinically relevant chemotherapy-induced neuropathic pain in rats.
Retrospective review and literature review OBJECTIVE.: To provide an update on The Cochrane Back and Neck (CBN) activities.
Transcribed ultraconserved regions are a novel class of long noncoding RNAs and are completely conserved in humans, rats, and mice. Transcribed ultraconserved regions 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 transcribed ultraconserved region 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 chronic constriction injury-induced pain behaviours and spinal neuronal sensitization. By contrast, the overexpression of spinal uc.153 produced pain behaviours and neuronal sensitization in naive mice. Moreover, we found that uc.153 participates in the regulation of neuropathic pain by negatively modulating the processing of pre-miR-182-5p. Collectively, our findings reveal an important role for uc.153 in pain modulation and provide a novel drug target for neuropathic pain therapy.
To identify the role of age and gender in analgesic and adverse effects after administering fentanyl products for breakthrough pain (BT), given in doses proportional to opioid doses given for background pain.