The journal of pain : official journal of the American Pain Society
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Sodium channel blockers such as lidocaine, lamotrigine, and carbamazepine can be effective in the treatment of neuropathic pain. Though not approved for neuropathic pain indications, tricyclic antidepressants are often considered first-line treatment for conditions such as post-herpetic neuralgia and diabetic neuropathy. Several tricyclic antidepressants have been shown to block peripheral nerve sodium channels, which may contribute to their antihyperalgesic efficacy. In this study, we compared the sodium channel-blocking potency of a number of antidepressants, including tricyclic antidepressants and selective serotonin reuptake inhibitors. All compounds tested inhibited Na(V)1.7 in a state- and use-dependent manner, with affinities for the inactivated state ranging from 0.24 micromol/L for amitriptyline to 11.6 micromol/L for zimelidine. The tricyclic antidepressants were more potent blockers of Na(V)1.7. Moreover, IC(50)s for block of the inactivated state for amitriptyline, nortriptyline, imipramine, desipramine, and maprotiline were in the range of therapeutic plasma concentrations for both the treatment of depression as well as neuropathic pain. By contrast, fluoxetine, paroxetine, mianserine, and zimelidine had IC(50)s for Na(V)1.7 outside their therapeutic concentration ranges and generally were not efficacious against post-herpetic neuralgia or diabetic neuropathy. These results suggest that block of peripheral nerve sodium channels may contribute to the antihyperalgesic efficacy of certain antidepressants. ⋯ Tricyclic antidepressants are often considered first-line treatment for neuropathic pain. Some tricyclic antidepressants block sodium channels, which may contribute to their antihyperalgesic efficacy. In the current study, we compared the potency of peripheral sodium channel blockade for several tricyclic antidepressants and selective serotonin reuptake inhibitors with their therapeutic efficacy.
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Animal models of neuropathic pain in which a peripheral nerve is damaged result in spontaneous activity in primary afferents that can be inhibited by intravenous administration of sodium channel blockers. Many of these compounds exhibit use-dependent block of sodium current, leading to the prediction that they should more readily inhibit neurons that fire at higher frequencies. This prediction was tested in 2 rat models of nerve injury, L5 spinal nerve section and sciatic nerve section. Sciatic nerve section produced average firing frequencies that were higher than spinal nerve section and often manifested as high-frequency bursting. Inhibition of firing by intravenous sodium channel blockers was longer lasting in this model. Within each model, higher frequency of firing did not translate into more effective block. In the spinal nerve section model, there was a robust inverse correlation between frequency and inhibition. Within the sciatic section model, only neurons that fired in rhythmic bursts were inhibited, and again, those firing at lower mean frequencies were more effectively inhibited. These results indicate that the efficacy of sodium channel blockers depends on the nature of the injury and the pattern of the resulting activity rather than simply the frequency of action potentials generated. ⋯ This study examines the ability of frequency-dependent sodium channel blockers to inhibit spontaneous firing of injured peripheral nerves in vivo. It outlines the conditions under which inhibition is more and less effective and will provide insight into conditions under which sodium channel blockers are likely to be therapeutically useful.
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Comparative Study Clinical Trial
Pain catastrophizing, response to experimental heat stimuli, and post-cesarean section pain.
This prospective study assessed the relation between pain catastrophizing, response to experimental pain stimuli, and pain perceived by women after elective cesarean sections. Forty-seven women who were scheduled for elective cesarean section were enrolled in the study. Magnitude estimation to suprathreshold phasic and tonic heat pain stimuli was assessed 1 or 2 days before surgery. Women completed the Pain Catastrophizing Scale after the heat stimuli and again on the first postoperative day. During the first and second postoperative days, perception of pain intensity was assessed by visual analog scale at each analgesia request. A multiple regression analysis revealed that pain on the first postoperative day was predicted by patient response to preoperative tonic heat stimuli (r(2) = .167, P = .008). Pain on the second postoperative day was predicted by preoperative pain catastrophizing (r(2) = .139, P = .021). No significant association was observed between preoperative response to heat stimuli or pain catastrophizing and the patient's analgesic consumption in the obstetrical ward. It is concluded that pain catastrophizing and response to experimental tonic heat pain correlate with post-cesarean section pain. ⋯ This article presents psychological and psychophysical measures that may be of help in the prediction of post-cesarean section pain. It may therefore contribute to the treatment of the sequelae of the most common major surgical procedure performed in women in their reproductive years.
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Transcutaneous electrical nerve stimulation (TENS) is a nonpharmacological method for pain management. Commercial TENS units differ in their waveform characteristics. However, effects of different waveforms on analgesia produced by TENS are unknown. Therefore, we compared effects of high-frequency TENS with different waveforms--asymmetric biphasic square and symmetric biphasic square--on inflammatory hyperalgesia. Paw withdrawal latency to heat (PWL) was assessed prior to inflaming the knee joint with 3% carrageenan/kaolin in rats. Four hours after induction of inflammation, PWL significantly decreased in all groups, indicating development of hyperalgesia. High-frequency TENS was then applied to the inflamed knee joint for 20 minutes while the rat was lightly anesthetized with halothane. TENS treatment with either the asymmetric or symmetric waveform significantly increased the PWL when compared with sham TENS. Thus, differences in waveform characteristics do not affect the anti-hyperalgesia produced by TENS. ⋯ This study shows that different waveforms of TENS do not affect analgesic efficacy. This suggests that clinicians can select different waveforms to provide comfort during treatment but that reduction in pain is not a factor for waveform selection.
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Randomized Controlled Trial Comparative Study Clinical Trial
Caffeine attenuates delayed-onset muscle pain and force loss following eccentric exercise.
This double-blind, placebo-controlled, repeated-measures experiment examined the effects of a 5 mg . kg(-1) body weight dose of caffeine on delayed-onset muscle pain intensity and force loss in response to 64 eccentric actions of the dominant quadriceps induced by electrical stimulation. Low caffeine-consuming college-aged females (n = 9) ingested caffeine or placebo 24 and 48 hours following electrically stimulated eccentric exercise of the quadriceps. One hour after ingestion, maximal voluntary isometric contractions (MVIC) and submaximal voluntary eccentric actions were used to determine force loss during activation of damaged quadriceps and whether caffeine attenuates muscle pain intensity. Pain intensity was measured using a 0 to 100 visual analog scale. Caffeine produced a large (12.7 raw visual analog scale [VAS] units; -48%; Cohen's d effect size = -0.88), statistically significant hypoalgesia during the MVIC (t = -2.52; df = 8; P = .036). The reduction in pain scores during submaximal voluntary eccentric movements was smaller (7.8 raw VAS units; -26%, d = -0.34), as was the increase in MVIC force (4.4%; d = 0.13). ⋯ Eccentric exercise occurs when skeletal muscles produce force while being lengthened. For example, the biceps brachii muscles act eccentrically when a cup of coffee is lowered from the mouth to a tabletop. This experiment found that caffeine (equal to approximately 2 cups of brewed coffee) could produce a large reduction in pain resulting from eccentric exercise-induced, delayed-onset muscle injury. This finding may improve the quality of life of individuals who experience skeletal muscle pain after engaging in unaccustomed, eccentrically biased exercise.