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Clinical Neurophysiology : Official... Oct 2023Chronic pain may lead to functional changes in several brain regions, including the primary motor cortex (M1). Our neurophysiological study aimed to probe M1 plasticity,...
OBJECTIVE
Chronic pain may lead to functional changes in several brain regions, including the primary motor cortex (M1). Our neurophysiological study aimed to probe M1 plasticity, through a non-invasive transcranial magnetic stimulation protocol, in a cohort of patients with chronic pain.
METHODS
Twenty patients with chronic pain (age ± SD: 62.9 ± 9.9) and 20 age- and sex-matched healthy controls (age ± SD: 59.6 ± 15.8) were recruited. Standardized scales were used for the evaluation of pain severity. Neurophysiological measures included laser-evoked potentials (LEPs) and motor-evoked potentials (MEPs) collected at baseline and over 60 minutes following a standardized Laser-paired associative stimulation (Laser-PAS) protocol.
RESULTS
LEPs and MEPs were comparable in patients with chronic pain and controls. The pain threshold was lower in patients than in controls. Laser-PAS elicited decreased responses in patients with chronic pain. The response to Laser-PAS was similar in subgroups of patients with different chronic pain phenotypes.
CONCLUSIONS
M1 plasticity, as tested by Laser-PAS, is altered in patients with chronic pain, possibly reflecting abnormal pain-motor integration processes.
SIGNIFICANCE
Chronic pain is associated with a disorder of M1 plasticity raising from abnormal pain-motor integration.
Topics: Humans; Chronic Pain; Motor Cortex; Transcranial Magnetic Stimulation; Evoked Potentials, Motor; Pain Threshold; Neuronal Plasticity
PubMed: 37595480
DOI: 10.1016/j.clinph.2023.07.010 -
Cephalalgia : An International Journal... Feb 2024Despite advances in neuroimaging and electrophysiology, cluster headache's pathogenesis remains unclear. This review will examine clinical neurophysiology studies,... (Review)
Review
BACKGROUND
Despite advances in neuroimaging and electrophysiology, cluster headache's pathogenesis remains unclear. This review will examine clinical neurophysiology studies, including electrophysiological and functional neuroimaging, to determine if they might help us construct a neurophysiological model of cluster headache.
RESULTS
Clinical, biochemical, and electrophysiological research have implicated the trigeminal-parasympathetic system in cluster headache pain generation, although the order in which these two systems are activated, which may be somewhat independent, is unknown. Electrophysiology and neuroimaging have found one or more central factors that may cause seasonal and circadian attacks. The well-known posterior hypothalamus, with its primary circadian pacemaker suprachiasmatic nucleus, the brainstem monoaminergic systems, the midbrain, with an emphasis on the dopaminergic system, especially when cluster headache is chronic, and the descending pain control systems appear to be involved. Functional connection investigations have verified electrophysiological evidence of functional changes in distant brain regions connecting to wide cerebral networks other than pain.
CONCLUSION
We propose that under the impact of external time, an inherited misalignment between the primary circadian pacemaker suprachiasmatic nucleus and other secondary extra- suprachiasmatic nucleus clocks may promote disturbance of the body's internal physiological clock, lowering the threshold for bout recurrence.
Topics: Humans; Cluster Headache; Suprachiasmatic Nucleus; Pain; Brain; Brain Stem
PubMed: 38415635
DOI: 10.1177/03331024231209317 -
European Journal of Pharmacology Dec 2023Transient receptor potential vanilloid 4 (TRPV4)-mediated astrocyte activation is critical to neuropathic pain. Pregabalin, a widely used drug to treat chronic pain, is...
BACKGROUNDS
Transient receptor potential vanilloid 4 (TRPV4)-mediated astrocyte activation is critical to neuropathic pain. Pregabalin, a widely used drug to treat chronic pain, is reported to lower the intracellular calcium level. However, the molecular mechanism by which pregabalin decreases the intracellular calcium level remains unknown. Purinergic P2Y receptor-a member of the G protein-coupled receptor (GPCR) family-regulates calcium-related signal transduction in astrocyte activation. We investigated whether P2Y receptor is involved in the pharmacological effects of pregabalin on neuropathic pain.
METHODS
Neuropathic pain was induced by chronic compression of the dorsal root ganglion (CCD) in rats. Paw withdrawal mechanical threshold (PWMT) was used for behavioral testing. Intracellular calcium concentration was measured using a fluorescent calcium indicator (Fluo-4 AM).
RESULTS
We found that P2Y receptor protein was upregulated and astrocytes were activated in the experimental rats after CCD surgery. Lipopolysaccharide (LPS) increased the intracellular calcium concentration and induced astrocyte activation in cultured astrocytes but was prevented via P2Y receptor inhibitor AR-C118925 or pregabalin. Furthermore, plasmid-mediated P2Y receptor overexpression induced an elevation of the intracellular calcium levels and inflammation in astrocytes, which was abolished by the TRPV4 inhibitor HC-067047. AR-C118925, HC-067047, and pregabalin relieved neuropathic pain and inflammation in rats after CCD surgery. Finally, plasmid-mediated P2Y receptor overexpression induced neuropathic pain in rats, which was abolished by pregabalin administration.
CONCLUSIONS
Pathophysiological variables that upregulated the P2Y receptor/TRPV4/calcium axis contribute to astrocyte activation in neuropathic pain. Pregabalin exerts an analgesic effect by inhibiting this pathway.
Topics: Rats; Animals; Pregabalin; Astrocytes; TRPV Cation Channels; Calcium; Neuralgia; Antineoplastic Agents; Calcium Signaling; Inflammation
PubMed: 37925132
DOI: 10.1016/j.ejphar.2023.176140 -
Journal of Cardiothoracic Surgery Nov 2023Postoperative analgesic management is an ongoing challenge. The pain threshold (PT) is an objective index that reflects the body's sensitivity to pain and can be used... (Observational Study)
Observational Study
BACKGROUND
Postoperative analgesic management is an ongoing challenge. The pain threshold (PT) is an objective index that reflects the body's sensitivity to pain and can be used for quantitative pain assessment. We hypothesized that the PT is correlated with postoperative pain and can thus be used to guide postoperative pain management.
METHODS
This study involved 93 patients who underwent thoracoscopic surgery from December 2019 to February 2020. The PT was measured with transcutaneous electrical stimulation before surgery (T) and at 1 h (T), 6 h (T), and 24 h (T) after surgery. The visual analogue scale (VAS) score was used to evaluate the severity of postoperative pain at the same time. The PT variation (PTV) after surgery was calculated as the ratio of the postoperative PT to preoperative PT.
RESULTS
The postoperative PT was higher than the preoperative PT and showed a downward trend within 24 h after surgery; the PTV also showed a downward trend within 24 h after surgery. PT-T was negatively correlated with VAS-T at rest and during motion (rest: VAS-Tr = - 0.274, P = 0.008; motion: VAS-Tr = - 0.298, P = 0.004). PTV-T was negatively correlated with VAS-T during motion (r = - 0.213, P = 0.04). Lower VAS-T scores (< 4) at rest and during motion were associated with higher PT-T (rest: t = 2.452, P = 0.016; motion: t = 2.138, P = 0.035). The intraoperative sufentanil dose was associated with a postoperative increase in PTV-T. Increased rescue analgesic administration was associated with PTV elevation. However, the incidence of dizziness in patients with moderate PTV-T was lower than that in patients with high or low PTV-T (χ = 8.297, P = 0.015).
CONCLUSIONS
The postoperative PT was higher than the preoperative PT and showed a downward trend within 24 h after surgery; PTV also showed a downward trend within 24 h after surgery. The PT and PTV were negatively correlated with the pain intensity at rest and during motion and were associated with perioperative analgesic consumption and the incidence of adverse events.
Topics: Humans; Pain Threshold; Thoracic Surgery; Acute Pain; Analgesics; Pain, Postoperative; Analgesics, Opioid
PubMed: 37964267
DOI: 10.1186/s13019-023-02424-w -
Osteoarthritis and Cartilage Oct 2023To examine whether pain sensitization is associated with hand and lower extremity function in people with hand osteoarthritis (OA) in the Nor-Hand study.
OBJECTIVE
To examine whether pain sensitization is associated with hand and lower extremity function in people with hand osteoarthritis (OA) in the Nor-Hand study.
DESIGN
Pain sensitization was assessed by pressure pain thresholds (PPTs) and temporal summation (TS). Hand function was assessed by Australian/Canadian Osteoarthritis Hand Index (AUSCAN) (range: 0-36), grip strength and Moberg pick-up test, and lower extremity function was assessed by Western Ontario and McMaster Universities Osteoarthritis Index (range: 0-68), 30-s chair stand test, and 40-m walk test. We examined whether sex-standardized PPT and TS values were cross-sectionally associated with measures of physical function using linear regression analyses. Beta coefficients were presented per sex-specific standard deviation of PPT and TS. The mediating effect of pain was examined by causal-inference based mediation analysis.
RESULTS
In 206 participants, higher PPTs at/near the hand, indicative of less peripheral and/or central pain sensitization, were associated with greater grip strength and better self-reported hand function (beta for PPT at finger joint on AUSCAN function: -1.41, 95% CI -2.40, -0.42). Higher PPTs at/near the hand, near the knee and at trapezius were associated with lower extremity function, although not statistically significant for all outcomes. Self-reported pain severity mediated the effect of PPT on self-reported function. TS was not associated with hand or lower extremity function.
CONCLUSION
Peripheral sensitization, and possibly central sensitization, was associated with impaired function. Effects of PPTs on self-reported function were mediated by self-reported pain, whereas there might be a direct effect of sensitization or effects through other mediators on performance-based function.
Topics: Male; Female; Humans; Australia; Canada; Pain; Osteoarthritis; Pain Threshold; Osteoarthritis, Knee
PubMed: 37495183
DOI: 10.1016/j.joca.2023.07.005 -
Musculoskeletal Science & Practice Aug 2023Evidence on the acute impact of high-intensity interval aerobic exercise on pain is scarce. This type of exercise might be perceived as increasing pain intensity and... (Randomized Controlled Trial)
Randomized Controlled Trial
Pain intensity and pain sensitivity are not increased by a single session of high-intensity interval aerobic exercise in individuals with chronic low back pain: A randomized and controlled trial.
BACKGROUND
Evidence on the acute impact of high-intensity interval aerobic exercise on pain is scarce. This type of exercise might be perceived as increasing pain intensity and pain sensitivity negatively impacting adherence. More evidence on the acute effects of high-intensity interval aerobic exercise in individuals with low back pain (LBP) is needed.
OBJECTIVES
To compare the acute effects of a single session of high-intensity interval aerobic exercise, continuous moderate-intensity aerobic exercise, and no exercise on pain intensity and pain sensitivity in patients with chronic non-specific LBP.
DESIGN
Randomized controlled trial with three arms.
METHOD
Participants were randomly assigned to one of three groups (i) continuous moderate-intensity aerobic exercise, ii) high-intensity interval aerobic exercise, and iii) no intervention. Measures of pain intensity and pressure pain threshold (PPT) at the lower back and at a distant body site (upper limb) were taken before and after 15 min of exercise.
RESULTS
Sixty-nine participants were randomized. A significant main effect of time was found for pain intensity (p = 0.011; η2p = 0.095) and for PPT at the lower back (p < 0.001; η2p = 0.280), but not a time versus group interaction (p > 0.05). For PPT at the upper limb, no main effect of time or interaction was found (p > 0.5).
CONCLUSIONS
Fifteen minutes of high-intensity interval aerobic exercise does not increase pain intensity or pain sensitivity compared to both moderate-intensity continuous aerobic exercise and no exercise, suggesting that high-intensity interval aerobic exercise can be used in clinical practice and patients reassured that it is unlikely to increase pain.
Topics: Humans; Pain Threshold; Pain Measurement; Low Back Pain; Exercise
PubMed: 37421759
DOI: 10.1016/j.msksp.2023.102824 -
Journal of Translational Medicine Aug 2023Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps...
BACKGROUND
Brachial plexus root avulsion (BPRA), a disabling peripheral nerve injury, induces substantial motoneuron death, motor axon degeneration and denervation of biceps muscles, leading to the loss of upper limb motor function. Acetylglutamine (N-acetyl-L-glutamine, NAG) has been proven to exert neuroprotective and anti-inflammatory effects on various disorders of the nervous system. Thus, the present study mainly focused on the influence of NAG on motor and sensory recovery after BPRA in rats and the underlying mechanisms.
METHODS
Male adult Sprague Dawley (SD) rats were subjected to BPRA and reimplantation surgery and subsequently treated with NAG or saline. Behavioral tests were conducted to evaluate motor function recovery and the mechanical pain threshold of the affected forelimb. The morphological appearance of the spinal cord, musculocutaneous nerve, and biceps brachii was assessed by histological staining. Quantitative real-time PCR (qRT‒PCR) was used to measure the mRNA levels of remyelination and regeneration indicators in myocutaneous nerves. The protein levels of inflammatory and pyroptotic indicators in the spinal cord anterior horn were measured using Western blotting.
RESULTS
NAG significantly accelerated the recovery of motor function in the injured forelimbs, enhanced motoneuronal survival in the anterior horn of the spinal cord, inhibited the expression of proinflammatory cytokines and pyroptosis pathway factors, facilitated axonal remyelination in the myocutaneous nerve and alleviated atrophy of the biceps brachii. Additionally, NAG attenuated neuropathic pain following BPRA.
CONCLUSION
NAG promotes functional motor recovery and alleviates neuropathic pain by enhancing motoneuronal survival and axonal remyelination and inhibiting the pyroptosis pathway after BPRA in rats, laying the foundation for the use of NAG as a novel treatment for BPRA.
Topics: Male; Rats; Animals; Rats, Sprague-Dawley; Neuralgia; Spinal Cord; Atrophy; Brachial Plexus
PubMed: 37612586
DOI: 10.1186/s12967-023-04399-7 -
Scandinavian Journal of Pain Jul 2023Conditioned pain modulation is a commonly used quantitative sensory test, measuring endogenous pain control. The temporal stability of the test is questioned, and there... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVES
Conditioned pain modulation is a commonly used quantitative sensory test, measuring endogenous pain control. The temporal stability of the test is questioned, and there is a lack of agreement on the effect of different pain conditions on the conditioned pain modulation response. Thus, an investigation of the temporal stability of a conditioned pain modulation test among patients suffering from persistent or recurrent neck pain is warranted. Further, an investigation into the difference between patients experiencing a clinically important improvement in pain and those not experiencing such an improvement will aid the understanding between changes in pain and the stability of the conditioned pain modulation test.
METHODS
This study is based on a randomized controlled trial investigating the effect of home stretching exercises and spinal manipulative therapy vs. home stretching exercises alone. As no difference was found between the interventions, all participants were studied as a prospective cohort in this study, investigating the temporal stability of a conditioned pain modulation test. The cohort was also divided into responders with a minimally clinically important improvement in pain and those not experiencing such an improvement.
RESULTS
Stable measurements of conditioned pain modulation were observed for all independent variables, with a mean change in individual CPM responses of 0.22 from baseline to one week with a standard deviation of 1.34, and -0.15 from the first to the second week with a standard deviation of 1.23. An Intraclass Correlation Coefficient (ICC3 - single, fixed rater) for CPM across the three time points yielded a coefficient of 0.54 (p<0.001).
CONCLUSIONS
Patients with persistent or recurrent neck pain had stable CPM responses over a 2 week course of treatment irrespective of clinical response.
Topics: Humans; Pain Threshold; Pain Measurement; Neck Pain; Prospective Studies; Pain Management
PubMed: 36869854
DOI: 10.1515/sjpain-2022-0084 -
Musculoskeletal Science & Practice Aug 2023This study aims to assess differences in clinical characteristics across healthy controls and migraine patients with (MNP) and without (MwoNP) neck pain.
AIMS
This study aims to assess differences in clinical characteristics across healthy controls and migraine patients with (MNP) and without (MwoNP) neck pain.
METHOD
This study assessed: headache frequency; headache disability index (HDI); central sensitization inventory (CSI); Hospital Anxiety (HADS-A) and Depression (HADS-D) scale; active range of motion (AROM); flexion rotation test (FRT); activation pressure score (APS); number of active/latent myofascial trigger points (MTrPs) in head/neck muscles; number of positive cervical vertebral segments (C1/C2) who reproduce migraine pain; wind-up ratio (WUR); mechanical pain threshold (MPT) and static pressure pain threshold (sPPT) over the trigeminal area; sPPT and dynamic PPT (dPPT) over the cervical area; sPPTs and MPT over the hand.
RESULTS
Compared to controls, MNP had: worse CSI, HADS-A, and HADS-D (all, p < 0.002); reduced AROM (flexion, extension, left lateral-flexion, and right-rotation), FRT, APS, and a higher number of MTrPs and positive cervical vertebral segments (all, p < 0.020); reduced trigeminal MPT and sPPT, cervical sPPT and dPPT, hand MPT and sPPT (all, p < 0.006). Compared to controls, MwoNP had: worse CSI, and HADS-A (all, p < 0.002); reduced AROM (flexion, and left lateral-flexion), FRT, APS, and a higher number of MTrPs and positive cervical vertebral segments (all, p < 0.017); reduced trigeminal MPT and cervical dPPT (all, p < 0.007). Compared to MwoNP, MNP had higher headache frequency, worse HDI and CSI (all, p < 0.006); reduced AROM (flexion, and right rotation) (all, p < 0.037); reduced cervical dPPT (all, p < 0.002).
CONCLUSION
MNP had worse headache characteristics, more pronounced cervical musculoskeletal impairments, enhanced signs and symptoms related to sensitization, and worse psychological burden compared to MwoNP.
Topics: Humans; Neck Pain; Migraine Disorders; Neck; Headache; Muscle, Skeletal
PubMed: 37344290
DOI: 10.1016/j.msksp.2023.102800 -
Journal of Lasers in Medical Sciences 2023Temporomandibular disorders (TMDs) are the most prevalent non-dental origin orofacial pain conditions affecting the temporomandibular joints (TMJs) and/or orofacial... (Review)
Review
The Effect of Photobiomodulation on Temporomandibular Pain and Functions in Patients With Temporomandibular Disorders: An Updated Systematic Review of the Current Randomized Controlled Trials.
Temporomandibular disorders (TMDs) are the most prevalent non-dental origin orofacial pain conditions affecting the temporomandibular joints (TMJs) and/or orofacial muscles. Photobiomodulation therapy (PBMT) is a conservative way to improve function and reduce symptoms in TMD patients. This systematic review was conducted to update evidence about the effects of PBMT on pain intensity, TMJ movements, electromyography (EMG) activity, pressure pain threshold (PPT), and TMJ sound in patients with TMDs. A systematic literature search was conducted in Web of Science, PubMed/Medline, and Scopus databases using appropriate keywords and specific strategies from January 2000 to September 2022. Data extraction was done based on the inclusion/exclusion criteria. A total of 40 studies were included. All included studies except one provided information on pain intensity; 27 studies showed a reduction in pain intensity in PBMT groups compared to control groups. Seven out of 15 studies, which reported maximum mouth opening (MMO), showed a greater MMO in PBMT groups than in placebo groups. In addition, the figures for passive maximum mouth opening (PMMO) and active maximum mouth opening (AMMO) in all the studies reporting PMMO and AMMO were higher in PBMT groups. In eight out of ten studies, lateral movement (LM) was greater in PBMT groups. Moreover, in three studies out of four, protrusive movement (PM) was reported to be greater in the PBMT group. Four out of nine studies showed a greater PPT in the PBMT group. Reduced TMJ sounds in the PBMT group were reported in two out of five studies. In addition, in most studies, no difference in EMG activity was detected between the two groups. This updated systematic review showed the promising effects of PBMT on the alleviation of pain and improvement in MMO. Using the infrared diode laser with a wavelength ranging between 780-980 nm, an energy density of<100 J/ cm, and an output power of≤500 mW for at least six sessions of treatment seems to be a promising option for treating mentioned TMDs signs and symptoms based on the previously reported findings.
PubMed: 37744015
DOI: 10.34172/jlms.2023.24