The journal of pain : official journal of the American Pain Society
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Chronic muscle pain is a major clinical problem that is often associated with fatigue. Conversely, chronic fatigue conditions are commonly associated with muscle pain. We tested the hypothesis that muscle fatigue enhances hyperalgesia associated with injection of acidic saline into muscle. We evaluated mechanical sensitivity of the paw (von Frey) in mice after 2 intramuscular injections of saline (20 microL; pH 4, pH 5, pH 6, pH 7.2) in a fatigue and a control group. To induce fatigue, mice were run for 2 h/day for 2 days prior to the first injection and 2 h/day for 2 days prior to the second injection. Muscle lactate, pCO(2), pO(2), creatinine kinase, phosphate, and histology were examined after the fatigue task and compared to a control group. Grip force was significantly decreased after 2 h of running indicating fatigue. The fatigue task did not induce muscle damage as there was no difference in muscle lactate, pCO(2), pO(2), creatinine kinase, phosphate, or histology. The fatigue task altered the dose-response relationship to intramuscular acidic saline injections. Mechanical hyperalgesia was observed in both fatigue and control groups after intramuscular injection of pH 4.0, but only the fatigue group after injection of pH 5. Neither the fatigue nor the control group developed hyperalgesia in response to intramuscular injection of pH 6 or pH 7.2. In conclusion, fatigue modified the susceptibility of mice to acid injection of pH 5.0 to result in mechanical hyperalgesia after 2 injections of pH 5.0. The fatigue task did not produce measurable changes in the muscle tissue suggesting a central mechanism mediating the enhancement of hyperalgesia. ⋯ These data therefore show that muscle fatigue can enhance the likelihood that one develops pain to a mild insult. Clinically, this could relate to the development of pain from such conditions as repetitive strain injury, and may relate to the interrelationship between chronic pain and fatigue.
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This cross-sectional study describes chronic pain in 94 persons with multiple sclerosis residing in the community. The characteristics of chronic pain, pain-related disability, pain treatments, barriers to health care, and impact on quality of life were examined. Sixty-four percent of participants reported chronic pain; of these, 60% had dysesthetic pain and 70% had episodic increases in pain. The mean numerical pain intensity rating score was moderate (5). Chronic Pain Grade was used to classify severity of pain, using scores for items for pain intensity and pain-related disability. Those in the higher pain grades had more disability and recorded more health care visits (P = .06) (not significant because of small sample size). Effective pain management techniques included analgesic medication and physical measures as reported by 54% and 44% participants, respectively. Participants' perceived barriers to health care included environmental and personal factors. Those with multiple sclerosis and pain, compared with those with no pain, showed a significant difference in the domain of psychological well-being scores (P = .01) on the Assessment of Quality of Life scale. Additionally, the domains of independent living (P = .009) and total scores (P = .04) showed better quality of life in participants with lower pain grades. Improved understanding of chronic pain in this population may facilitate early identification for timely intervention and minimize pain-related disability. ⋯ This article describes chronic pain in persons with multiple sclerosis living in the community. The information regarding pain prevalence, pain-related disability, and impact on quality of life provides insight into the complex multidimensional pain experience. Improved understanding of pain and early intervention may contribute to the overall well-being and decrease pain-related disability in this population.
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The goal of this study was to determine the intra- and interday reliability of pressure pain thresholds (PPT) in the upper extremity and torso of asymptomatic women. Nineteen healthy women (20-39 years) with no underlying musculoskeletal problems had 3 PPT trials performed on 8 different locations in the upper extremity and torso over 4 consecutive days. The test-retest reliability of PPT values was robust and highly consistent over the 4 days. The PPT intraclass correlations (ICC) were highly consistent and repeatable over the 4 days of testing (day 1: ICC = 0.94; day 2: ICC = 0.96; day 3: ICC = 0.97 and day 4: ICC = 0.96). When compared with baseline measurements obtained on day 1, the PPT values were significantly lower (P < .05) on days 2, 3, and 4 at all 8 locations. Although the PPT test-retest reliability is robust and consistent throughout the 4 days, there appears to be a similar overall decline in the magnitude of the absolute PPT response at each of the 8 locations. A specific explanation for this greater overall sensitivity in PPTs at all 8 locations is lacking; however, a centrally mediated alteration in pressure/pain sensation could contribute to the overall trend observed in this study. ⋯ PPT measurements of the upper limb and torso will be significantly lower with repeated measures over a short period time. A standardized evaluation grid should be included in baseline so as to accurately evaluate the progression in shoulder rehabilitation in women with shoulder dysfunction.
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The antidepressant amitriptyline is used as an adjuvant in the treatment of chronic pain. Among its many actions, amitriptyline blocks Na+ channels and nerves in several animal and human models. As perioperative intravenous lidocaine has been suggested to decrease postoperative pain, amitriptyline, because of its longer half-life time, might be more useful than lidocaine. However, the use of intravenous amitriptyline is not approved by the US Food and Drug Administration. We therefore investigated the adverse effects of preoperative intravenous amitriptyline in a typical phase 1A trial. After obtaining written Food and Drug Administration and institutional review board approval, we obtained written consent for preoperative infusion of amitriptyline in an open-label, dose-escalating design (25, 50, and 100 mg, n=5 per group). Plasma levels of amitriptyline/nortriptyline were determined, and adverse effects were recorded in a predetermined symptom list. Infusion of 25 and 50 mg amitriptyline appears to be well tolerated; however, the study was terminated when 1 subject in the 100-mg group developed severe bradycardia. Intravenous infusion of amitriptyline (25 to 50 mg over 1 hour) did not create side effects beyond dry mouth and drowsiness, or dizziness, in 2 of our 10 otherwise healthy participants receiving the 25- to 50-mg dose. An appropriately powered future trial is necessary to determine a potential role of amitriptyline in decreasing postoperative pain. ⋯ Amitriptyline potently blocks the persistently open Na+ channels, which are known to be instrumental in various pain states. As this occurs at very low plasma concentrations, a single preoperative intravenous infusion of amitriptyline could provide long-lasting pain relief and decrease the incidence of chronic pain.
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The present study was undertaken to determine the role of P2X3 receptor (P2X3R) on heat hyperalgesia in a newly developed rat model of trigeminal neuropathic pain. The unilateral infraorbital nerve (IoN) was partially ligated by 6-0 silk. To assess heat sensitivity, a vibrissal pad (VP) was placed on a hot plate and the latency until the rats withdrew their head was measured. Mechanical sensitivity of VP was also assessed by the use of von Frey filament. Both heat and mechanical hyperalgesia were observed at the VP ipsilateral to the IoN ligation. The latency to heat stimuli was prolonged after subcutaneous administration of pyridoxal-phosphate-6-azophenyl-2',4'-disulfonic acid (PPADS, P2X1,2,3,5,7,1/5,2/3R antagonist) and 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5'-triphosphate (TNP-ATP, P2X1,3,2/3,1/5R antagonist). The latency was shortened after administration of alpha,beta-methylene ATP (alpha,beta-meATP, P2X1,3,2/3R agonist), although no changes appeared after administration of beta,gamma-methylene-L-ATP (beta,gamma-me-L-ATP, P2X1R agonist). The protein gene product-9.5 and calcitonin gene-related peptide immunoreactive nerve fibers significantly decreased in the VP skin of ipsilateral to the IoN ligation. In the ipsilateral trigeminal ganglion, the number of P2X3-immunoreactive neurons significantly increased in the small cell group. In this study, we developed an experimental model of trigeminal neuropathic pain by partial ligation of IoN, which produced heat and mechanical hyperalgesia in the VP. Pharmacological and immunohistochemical studies revealed that the P2X3R plays an important role in the heat hyperalgesia observed in this model. ⋯ The study describes the development of a novel model of trigeminal neuropathic pain. Heat hyperalgesia in this model was inhibited by peripheral injection of P2XR antagonists. The results suggest that P2X3R is a potential target for development of a novel therapy for trigeminal neuropathic pain.