Predicting Individual Pain Sensitivity Using a Novel Cortical Biomarker Signature.

Importance: Biomarkers would greatly assist decision-making in the diagnosis, prevention, and treatment of chronic pain.

Objective: To undertake analytical validation of a sensorimotor cortical biomarker signature for pain consisting of 2 measures: sensorimotor peak alpha frequency (PAF) and corticomotor excitability (CME).

Design, Setting, And Participants: This cohort study at a single center (Neuroscience Research Australia) recruited participants from November 2020 to October 2022 through notices placed online and at universities across Australia.

Green Light Exposure Reduces Primary Hyperalgesia and Proinflammatory Cytokines in a Rodent Model of Knee Osteoarthritis: Shedding Light on Sex Differences.

Knee osteoarthritis (OA) often causes chronic pain that disproportionately affects females. Proinflammatory cytokines TNF-α, IL-1β, and IL-6 are key effectors of OA pathological changes. Green light shows potential as an alternative intervention for various pain conditions.

Age- and Sex-Dependent Effects of Moderate Exercise on Endogenous Pain Inhibition in Rats.

Diffuse noxious inhibitory controls (DNICs), or the pain inhibits pain phenomenon, refer to reduced pain-like behaviors that are displayed following a noxious conditioning stimulus located far from the test stimulus and have also been referred to as "descending control of nociception" when measured in awake-behaving animals. In this study, we sought to determine the impact of moderate long-term exercise on the DCN response and determine if this effect differed across age and sex. After a six-week exercise program consisting of 30 min of moderate treadmill running 5 days a week, the animals' forepaws were injected with capsaicin, and DCN responses were assessed using thermal withdrawal latencies of the hind paw.

Forced swim stress exacerbates inflammation-induced hyperalgesia and oxidative stress in the rat trigeminal ganglia.

This study investigates the impact of combining psychophysical stress, induced by forced swim (FSS), with masseter inflammation on reactive oxygen species (ROS) production in trigeminal ganglia (TG), TRPA1 upregulation in TG, and mechanical hyperalgesia. In a rat model, we demonstrate that FSS potentiates and prolongs CFA-induced ROS upregulation within TG. The ROS levels in CFA combined with FSS group surpass those in the CFA-only group on days 4 and 28 post-treatment.

Inflammation, brain connectivity, and neuromodulation in post-traumatic headache.

Post-traumatic headache (PTH) is a debilitating condition that affects individuals with different levels of traumatic brain injury (TBI) severity. The difficulties in developing an effective treatment are related to a lack of understanding the complicated mechanisms and neurobiological changes in brain function after a brain injury. Preclinical studies have indicated that peripheral and central sensitization of the trigeminal nociceptive pathways contributes to PTH.

Sex differences in visceral sensitivity and brain activity in a rat model of comorbid pain: a longitudinal study.

Temporomandibular disorder (TMD) and irritable bowel syndrome (IBS) are 2 chronic overlapping pain conditions (COPCs) that present with significant comorbidity. Both conditions are more prevalent in women and are exacerbated by stress. While peripheral mechanisms might contribute to pain hypersensitivity for each individual condition, mechanisms underlying the comorbidity are poorly understood, complicating pain management when multiple conditions are involved.

Intraganglionic reactive oxygen species mediate inflammatory pain and hyperalgesia through TRPA1 in the rat.

Reactive oxygen species (ROS) are generated in nociceptive pathways in response to inflammation and injury. ROS are accumulated within the sensory ganglia following peripheral inflammation, but the functional role of intraganlionic ROS in inflammatory pain is not clearly understood. The aims of this study were to investigate whether peripheral inflammation leads to prolonged ROS accumulation within the trigeminal ganglia (TG), whether intraganglionic ROS mediate pain hypersensitivity via activation of TRPA1, and whether TRPA1 expression is upregulated in TG during inflammatory conditions by ROS.

Time of Day Influences Psychophysical Measures in Women With Burning Mouth Syndrome.

Burning mouth syndrome (BMS) is a chronic orofacial pain condition that mainly affects postmenopausal women. BMS type I patients report little to no spontaneous pain in the morning and increases in pain through the day, peaking in the afternoon. Quantitative sensory testing (QST) findings from BMS type 1 patients are inconsistent as they fail to capture this temporal variation.

Pain modulatory network is influenced by sex and age in a healthy state and during osteoarthritis progression in rats.

Old age and female sex are risk factors for the development of osteoarthritis (OA) and chronic pain. We investigated the effects of sex and age on pain modulatory networks in a healthy state and during OA progression. We used functional MRI to determine the effects of sex and age on periaqueductal gray functional connectivity (PAG FC) in a healthy state (pre-OA) and during the early and late phases of monosodium iodoacetate-induced OA in rats.

Effects of photobiomodulation therapy on neuropathic pain in rats: evaluation of nociceptive mediators and infrared thermography.

Nerve injury induces release of peptides and upregulation of receptors such as substance P and transient receptor potential receptor V1 (TRPV1), which contribute to the development and maintenance of chronic pain. Photobiomodulation therapy (PBMT) is a nonpharmacological strategy that promotes tissue repair and reduces pain and inflammation. However, the molecular basis for PBMT effects on neuropathic pain is still unclear.

Brain networks and endogenous pain inhibition are modulated by age and sex in healthy rats.

Endogenous pain inhibition is less efficient in chronic pain patients. Diffuse noxious inhibitory control (DNIC), a form of endogenous pain inhibition, is compromised in women and older people, making them more vulnerable to chronic pain. However, the underlying mechanisms remain unclear.

Neuroimaging of pain in animal models: a review of recent literature.

Neuroimaging of pain in animals allows us to better understand mechanisms of pain processing and modulation. In this review, we discuss recently published brain imaging studies in rats, mice, and monkeys, including functional magnetic resonance imaging (MRI), manganese-enhanced MRI, positron emission tomography, and electroencephalography. We provide an overview of innovations and limitations in neuroimaging techniques, as well as results of functional brain imaging studies of pain from January 1, 2016, to October 10, 2018.

Age and Sex Differences in Acute and Osteoarthritis-Like Pain Responses in Rats.

In this study, we investigated age and sex differences in acute and chronic pain in rats. Groups of young (3-6 months) and aged (20-24 months) male and female Fischer 344 rats were used to assess basal thermal and mechanical thresholds, capsaicin-induced acute nocifensive responses and c-Fos expression in the spinal cord, and monoiodoacetate (MIA)-induced knee osteoarthritis (OA)-like pain responses. There was a significant sex, but not age, effect on thermal threshold on the hindpaw and mechanical threshold on the knee joint.

Do chronic pain and comorbidities affect brain function in sickle cell patients? A systematic review of neuroimaging and treatment approaches.

Sickle cell disease (SCD) is a medical condition in which chronic pain is common and negatively impacts psychosocial function and quality of life. Although the brain mechanisms underlying chronic pain are well studied in other painful conditions, the brain mechanisms underlying chronic pain and the associated psychosocial comorbidities are not well established in SCD. A growing literature demonstrates the effect of treatment of chronic pain, including pharmacological and nonpharmacological treatments, on brain function.

Anti-NGF treatment can reduce chronic neuropathic pain by changing peripheral mediators and brain activity in rats.

Neuropathic pain is driven by abnormal peripheral and central processing, and treatments are insufficiently effective. Antibodies against nerve growth factor (anti-NGF) have been investigated as a potent analgesic treatment for numerous conditions. However, the peripheral and brain effects of anti-NGF in neuropathic pain remain unknown.

Diffuse noxious inhibitory controls and brain networks are modulated in a testosterone-dependent manner in Sprague Dawley rats.

Diffuse noxious inhibitory control (DNIC), which involves endogenous pain modulation, has been investigated as a potential mechanism for the differences in pain modulation observed between men and women, though the literature shows contradictory findings. We used a capsaicin-induced DNIC behavioral assay and resting state functional magnetic resonance imaging (rsfMRI) to assess the effect of testosterone on pain modulation and related brain circuitry in rats. We hypothesized that testosterone is required for DNIC that leads to efficient pain inhibition by increasing descending pain modulation.

Non-pharmacological treatment affects neuropeptide expression in neuropathic pain model.

Chronic constriction injury (CCI) of the sciatic nerve elicits changes in neuropeptide expression on the dorsal root ganglia (DRG). The neural mobilization (NM) technique is a noninvasive method that has been proven clinically effective in reducing pain. The aim of this study was to analyze the expression of substance P, transient receptor potential vanilloid 1 (TRPV1) and opioid receptors in the DRG of rats with chronic constriction injury and to compare it to animals that received NM treatment.

Neural Mobilization Treatment Decreases Glial Cells and Brain-Derived Neurotrophic Factor Expression in the Central Nervous System in Rats with Neuropathic Pain Induced by CCI in Rats.

. Glial cells are implicated in the development of chronic pain and brain-derived neurotropic factor (BDNF) released from activated microglia contributes to the nociceptive transmission. Neural mobilization (NM) technique is a method clinically effective in reducing pain sensitivity.

Estrogen-dependent visceral hypersensitivity following stress in rats: An fMRI study.

We used functional MRI and a longitudinal design to investigate the brain mechanisms in a previously reported estrogen-dependent visceral hypersensitivity model. We hypothesized that noxious visceral stimulation would be associated with activation of the insula, anterior cingulate cortex, and amygdala, and that estrogen-dependent, stress-induced visceral hypersensitivity would both enhance activation of these regions and recruit activation of other brain areas mediating affect and reward processing. Ovariectomized rats were treated with estrogen (17 β-estradiol, E2) or vehicle (n = 5 per group) and scanned in a 7T MRI at three different time points: pre-stress (baseline), 2 days post-stress, and 18 days post-stress.

LOW BONE MINERAL DENSITY IN BRAZILIAN PATIENTS AT DIAGNOSIS OF CELIAC DISEASE.

Background: Low bone mineral density is considered an extra-intestinal manifestation of celiac disease with reduced bone mass, increased bone fragility, and risk of fractures. Celiac disease is considered a condition at high risk for secondary osteoporosis and the evaluation of bone density is very important in the clinical management of these patients.

Objective: The present study aimed to investigate bone alterations in celiac patients from Curitiba, South Region of Brazil at diagnosis, correlating the findings with age and gender.

Neural mobilization promotes nerve regeneration by nerve growth factor and myelin protein zero increased after sciatic nerve injury.

Neurotrophins are crucial in relation to axonal regrowth and remyelination following injury; and neural mobilization (NM) is a noninvasive therapy that clinically is effective in neuropathic pain treatment, but its mechanisms remains unclear. We examined the effects of NM on the regeneration of sciatic nerve after chronic constriction injury (CCI) in rats. The CCI was performed on adult male rats, submitted to 10 sessions of NM, starting 14 days after CCI.

The neural mobilization technique modulates the expression of endogenous opioids in the periaqueductal gray and improves muscle strength and mobility in rats with neuropathic pain.

Background: The neural mobilization (NM) technique is a noninvasive method that has been proven to be clinically effective in reducing pain; however, the molecular mechanisms involved remain poorly understood. The aim of this study was to analyze whether NM alters the expression of the mu-opioid receptor (MOR), the delta-opioid receptor (DOR) and the Kappa-opioid receptor (KOR) in the periaqueductal gray (PAG) and improves locomotion and muscle force after chronic constriction injury (CCI) in rats.

Methods: The CCI was imposed on adult male rats followed by 10 sessions of NM every other day, starting 14 days after the CCI injury.

Neural mobilization reverses behavioral and cellular changes that characterize neuropathic pain in rats.

Background: The neural mobilization technique is a noninvasive method that has proved clinically effective in reducing pain sensitivity and consequently in improving quality of life after neuropathic pain. The present study examined the effects of neural mobilization (NM) on pain sensitivity induced by chronic constriction injury (CCI) in rats. The CCI was performed on adult male rats, submitted thereafter to 10 sessions of NM, each other day, starting 14 days after the CCI injury.