The journal of pain : official journal of the American Pain Society
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There is lack of evidence that topical application of an anti-inflammatory reagent could reduce pain due to intervertebral foramen (IVF) inflammation (IVFI). We investigated analgesic effects and underlying mechanisms of topical application of a compound ibuprofen cream (CIC) onto the surface of back skin covering the inflamed L(5) IVF in a rat model. Repetitive CIC treatment (~.54 g each treatment daily for 5 consecutive days) significantly reduces severity and duration of IVFI-induced thermal hyperalgesia and mechanical allodynia by 80 to 100% and 50 to 66%, respectively. Electrophysiological studies and Western blot analysis demonstrated that CIC treatment significantly inhibited hyperexcitability of the inflamed dorsal root ganglion (DRG) neurons and upregulation of Nav1.7 and Nav1.8 protein, respectively. Pathological manifestations of the inflamed DRG were also markedly improved following CIC treatment. Further, in the inflamed DRGs, phosphorylation and expression of transcription factor NF-κB and pro-inflammatory enzyme cyclooxygenase-2 (COX-2) were significantly increased, while a cytokine IL-1β level was increased. IVFI-induced upregulation of these molecules was significantly inhibited by CIC treatment. This study provides evidence that an anti-inflammatory reagent can be used topically to suppress pain due to IVFI and/or DRG inflammation through inhibition of sensory neuron hyperexcitability and the immune and inflammatory responses. ⋯ This study suggests a convenient and safe clinical intervention for treating pain due to intervertebral foramen inflammation and similar syndromes.
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Genetic variations in the catechol-O-methyltransferase (COMT) gene have been associated with experimental pain and risk of chronic pain development, but no studies have examined genetic predictors of neck pain intensity and other patient characteristics after motor vehicle collision (MVC). We evaluated the association between COMT genotype and acute neck pain intensity and other patient characteristics in 89 Caucasian individuals presenting to the emergency department (ED) after MVC. In the ED in the hours after MVC, individuals with a COMT pain vulnerable genotype were more likely to report moderate-to-severe musculoskeletal neck pain (76 versus 41%, RR = 2.11 (1.33-3.37)), moderate or severe headache (61 versus 33%, RR = 3.15 (1.05-9.42)), and moderate or severe dizziness (26 versus 12%, RR = 1.97 (1.19-3.21)). Individuals with a pain vulnerable genotype also experienced more dissociative symptoms in the ED, and estimated a longer time to physical recovery (median 14 versus 7 days, P = .002) and emotional recovery (median 8.5 versus 7 days, P = .038). These findings suggest that genetic variations affecting stress response system function influence the somatic and psychological response to MVC, and provide the first evidence of genetic risk for clinical symptoms after MVC. ⋯ The association of COMT genotype with pain symptoms, psychological symptoms, and recovery beliefs exemplifies the pleiotropic effects of stress-related genes, which may provide the biological substrate for the biopsychosocial model of post-MVC pain. The identification of genes associated with post-MVC symptoms may also provide new insights into pathophysiology.
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The present study addresses the question whether pain-intensity ratings and skin conductance responses (SCRs) are able to detect different intensities of phasic painful stimuli and to determine the reliability of this discrimination. For this purpose, 42 healthy participants of both genders were assigned to either electrical, mechanical, or laser heat-pain stimulation (each n = 14). A whole range of single brief painful stimuli were delivered on the right volar forearm of the dominant hand in a randomized order. Pain-intensity ratings and SCRs were analyzed. Using generalizability theory, individual and gender differences were the main contributors to the variability of both intensity ratings and SCRs. Most importantly, we showed that pain-intensity ratings are a reliable measure for the discrimination of different pain stimulus intensities in the applied modalities. The reliability of SCR was adequate when mechanical and heat stimuli were tested but failed for the discrimination of electrical stimuli. Further studies are needed to reveal the reason for this lack of accuracy for SCRs when applying electrical pain stimuli. ⋯ Our study could help researchers to better understand the relationship between pain and activation of the sympathetic nervous system. Pain researchers are furthermore encouraged to consider individual and gender differences when measuring pain intensity and the concomitant SCRs in experimental settings.
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Abnormalities of central pain processing play an important role in the pathophysiology of fibromyalgia (FM). The aims of the present study were to: 1) evaluate habituation of laser-evoked potentials (LEP) to repeated painful stimulation of 1 tender and 2 nontender points; and 2) determine correlations between LEP abnormalities and major clinical features of FM. Fourteen consecutive FM outpatients and 13 normal controls were included. LEP were recorded from scalp designations Fz, Cz, Pz, T3, and T4. The dorsum of the right hand, the right supra-orbital zone, and the right knee (a tender point in all patients) were subjected to repeated CO2 laser stimuli. For each stimulation site, recordings were obtained for 3 consecutive series of 20 stimuli. The 3 main findings in FM patients were: 1) an increased amplitude of vertex LEP and subjective laser pain; 2) decreased habituation of vertex LEP and subjective laser pain; and 3) a correlation between reduced N2 wave habituation and the severity of self-reported depressive symptoms. As with other chronic pain syndromes, the pathophysiology of FM may involve a generalized increase in the perception of painful stimuli and reduced habituation of the sensory cortex. ⋯ Reduced habituation of cortical responses to laser stimuli in FM patients suggests alterations in the pattern of cortical excitability. This is facilitated by depressive symptoms and abnormalities in central neurotransmission. These findings provide further support for the use of medications with effects on the central nervous system in the management of FM.
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We evaluated the effectiveness of intrathecal antagonists of α1- (WB4101) and α2- (idazoxan) adrenoceptors and serotonergic (methysergide), opioid (naloxone), muscarinic (atropine), GABA(A) (bicuculline) and GABA(B) (phaclofen) receptors in blocking 2- or 100-Hz electroacupuncture (EA)-induced analgesia (EAIA) in the rat tail-flick test. EA was applied bilaterally to the Zusanli and Sanyinjiao acupoints in lightly anesthetized rats. EA increased tail-flick latency, where the effect of 2-Hz EA lasted longer than that produced by 100-Hz EA. The 2-Hz EAIA was inhibited by naloxone or atropine, was less intense and shorter after WB4101 or idazoxan, and was shorter after methysergide, bicuculline, or phaclofen. The 100-Hz EAIA was less intense and shorter after naloxone and atropine, less intense and longer after phaclofen, shorter after methysergide or bicuculline, and remained unchanged after WB4101 or idazoxan. We postulate that the intensity of the effect of 2-Hz EA depends on noradrenergic descending mechanisms and involves spinal opioid and muscarinic mechanisms, whereas the duration of the effect depends on both noradrenergic and serotonergic descending mechanisms, and involves spinal GABAergic modulation. In contrast, the intensity of 100-Hz EAIA involves spinal muscarinic, opioid, and GABA(B) mechanisms, while the duration of the effects depends on spinal serotonergic, muscarinic, opioid, and GABA(A) mechanisms. ⋯ The results of this study indicate that 2- and 100-Hz EA induce analgesia in the rat tail-flick test activating different descending mechanisms at the spinal cord level that control the intensity and duration of the effect. The adequate pharmacological manipulation of such mechanisms may improve EA effectiveness for pain management.