ABSTRACT: 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. PERSPECTIVE: 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.
Journal of Pain 10/2007; 8(9):692-9. · 4.93 Impact Factor
ABSTRACT: To determine the release pattern of serotonin and noradrenaline in the spinal cord in response to transcutaneous electric nerve stimulation (TENS) delivered at low or high frequency.
Prospective randomized allocation of 3 treatments.
Male Sprague-Dawley rats (weight range, 250-350 g).
Knee joints of rats were inflamed with a mixture of 3% carrageenan and 3% kaolin for 24 hours prior to placement of push-pull cannulae into the dorsal horn of the spinal cord. Push-pull samples were collected in 10-minute intervals before, during, and after treatment with low-frequency TENS (4 Hz), high-frequency TENS (100 Hz), or sham TENS. TENS was applied to the inflamed knee joint for 20 minutes at sensory intensity and 100-mus pulse duration. Push-pull samples were analyzed for serotonin and noradrenaline by high performance liquid chromatography with coulemetric detection.
Spinal concentrations of serotonin and noradrenaline.
Low-frequency TENS significantly increased serotonin concentrations during and immediately after treatment. There was no change in serotonin with high-frequency TENS, nor was there a change in noradrenaline with low- or high-frequency TENS.
Low-frequency TENS releases serotonin in the spinal cord to produce antihyperalgesia by activation of serotonin receptors.
Archives of Physical Medicine and Rehabilitation 09/2006; 87(8):1137-40. · 2.28 Impact Factor
ABSTRACT: Endogenous opioid peptides, enkephalins and endomorphins, are located in key regions involved in pain transmission and analgesia, including the spinal cord. These endogenous peptides activate opioid receptors to produce analgesia and reduce pain. We describe a new method to measure enkephalin and endomorphins by high performance liquid chromatography with electrochemical detection. This method allows use of a small sample volume to measure met-enkephalin, leu-enkephalin, endomorphin-1 and endomorphin-2 simultaneously. Using push-pull perfusion of the spinal cord, there were detectable concentrations of met-enkephalin, leu-enkephalin, and endomorphin-2. Further infusion of 100mM potassium chloride evoked release of met-enkephalin and endomorphin-2 but not leu-enkephalin. Thus, we have developed a method to simultaneously measure enkephalins and endomorphins in small sample volume that allows measurement of these opioid peptides in vivo.
Journal of Neuroscience Methods 02/2006; 150(1):74-9. · 1.98 Impact Factor