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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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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The reports on pain perception among former heroin addicts receiving methadone maintenance treatment (MMT) vary with regard to pain and intolerance threshold, and perception of suprathreshold stimuli has not been previously evaluated. Our aim was to systematically assess perception of threshold and suprathreshold noxious and innocuous stimuli with special attention to the effect of MMT dose and the presence of chronic pain. Noxious and innocuous, thermal and mechanical thresholds and ratings of suprathreshold heat-pain stimuli were measured among 31 MMT subjects receiving high and low MMT dose, with and without chronic pain, and in 17 healthy controls. The characteristics of chronic pain were also evaluated. MMT dose and chronic pain differentially affected pain perception. Whereas MMT dose did not affect thresholds, chronic pain MMT subjects exhibited increased pain threshold and pain-free MMT subjects exhibited decreased pain threshold compared with controls. MMT in general was associated with decreased perception of suprathreshold pain; however, MMT subjects with chronic pain exhibited increased suprathreshold pain ratings. It appears that subjects receiving MMT are hyperalgesic but that chronic pain in these subjects interferes with threshold measurements, inducing an apparent hypoalgesia. On the other hand, chronic pain reduces the analgesic effect of methadone seen in pain-free MMT subjects, amplifying suprathreshold pain perception. Factors such as chronic pain and MMT dose should be taken into account in future studies on pain perception in this population. ⋯ We show that the presence of chronic pain and methadone dose significantly affects perception of pain in former heroin addicts receiving MMT. Studying the alteration in pain perception in these subjects may contribute to understanding the high rates of chronic pain among them and may promote better treatment.
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Within a 2-year period in the 1940s, 2 Boston physicians published dramatically opposing views on the underlying nature of a syndrome now known as complex regional pain syndrome (CRPS). Evans suggested, in several papers in 1946-1947, that sympathetic reflexes maintain pain and dystrophy in affected limbs. Foisie, in 1947, suggested arterial vasospasms were key in the etiology of this pain syndrome. Evans' hypothesis established the nomenclature for this syndrome for 60 years, and his term, "reflex sympathetic dystrophy," guided clinical treatment and research activities over the same period. Foisie's proposed nomenclature was unrecognized, and had virtually no impact on the field. Recent evidence suggests that Evans' contribution to the field may have in fact led clinicians and researchers astray all those years. This focus article on CRPS compares recent observations with these 2 earlier theories and asks the question-what if we had adopted Foisie's nomenclature from the beginning? ⋯ This article discusses 2 opposing historical views on the etiology of what is now known as CRPS, and how they affected nomenclature, research, and clinical therapy in subsequent decades. This focus article may help researchers and clinicians realize the importance of syndrome names, and how they may inadvertently misdirect research and treatment.
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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.