Spinal cord stimulation-induced analgesia: electrical stimulation of dorsal column and dorsal roots attenuates dorsal horn neuronal excitability in neuropathic rats.

BACKGROUND: The sites of action and cellular mechanisms by which spinal cord stimulation reduces neuropathic pain remain unclear. METHODS: We examined the effect of bipolar electrical-conditioning stimulation (50 Hz, 0.2 ms, 5 min) of the dorsal column and lumbar dorsal roots on the response properties of spinal wide dynamic range (WDR) neurons in rats after L5 spinal nerve injury. The conditioning stimulation intensity was set at the lowest current that evoked a peak antidromic sciatic Aα/ß-compound action potential without inducing an Aδ- or C-compound action potential. RESULTS: Within 15 min of the dorsal column or root conditioning stimulation, the spontaneous activity rate of WDR neurons was significantly reduced in nerve-injured rats. Conditioning stimulation also significantly attenuated WDR neuronal responses to mechanical stimuli in nerve-injured rats and inhibited the C-component of the neuronal response to graded intracutaneous electrical stimuli applied to the receptive field in nerve-injured and sham-operated rats. It is noteworthy that dorsal column stimulation blocked windup of WDR neuronal response to repetitive intracutaneous electrical stimulation (0.5 Hz) in nerve-injured and sham-operated rats, whereas dorsal root stimulation inhibited windup only in sham-operated rats. Therefore, stimulation of putative spinal substrates at A-fiber intensities with parameters similar to those used by patients with spinal cord stimulators attenuated established WDR neuronal hyperexcitability in the neuropathic condition and counteracted activity-dependent increase in neuronal excitability (i.e., windup). CONCLUSIONS: These results suggest a potential cellular mechanism underlying spinal cord stimulation-induced pain relief. This in vivo model allows the neurophysiologic basis for spinal cord stimulation-induced analgesia to be studied.

Tart cherry anthocyanins suppress inflammation-induced pain behavior in rat.

The use of complementary and alternative medicine (CAM) has increased in the United States and more patients are seeking CAM therapies for control of pain. The present investigation tested the efficacy of orally administered anthocyanins extracted from tart cherries on inflammation-induced pain behavior in rats. Paw withdrawal latency to radiant heat and paw withdrawal threshold to von Frey probes were measured. The first set of experiments examined the effects of tart cherry anthocyanins (400 mg/kg) on the nociceptive behaviors and edema associated with inflammation induced by intraplantar injection of 1% carrageenan. These studies also included tests of motor coordination. The second set of experiments determined if tart cherry anthocyanins (15, 85, and 400 mg/kg) dose-dependently affected the inflammation induced by intraplantar injection of 25% complete Freund's adjuvant. We found that tart cherry extracts reduce inflammation-induced thermal hyperalgesia, mechanical hyperalgesia and paw edema. The suppression of thermal hyperalgesia was dose-dependent and the efficacy of highest dose (400 mg/kg) was similar to indomethacin (5 mg/kg). The highest dose anthocyanin (400 mg/kg) had no effects on motor function. These data suggest that tart cherry anthocyanins may have a beneficial role in the treatment of inflammatory pain. The antihyperalgesic effects may be related to the anti-inflammatory and antioxidant properties of anthocyanins. A better understanding of the modulatory role of dietary constituents and phytonutrients on pain will offer further therapeutic options for treating patients with persistent and chronic pain conditions.

Analgesic effects of a soy-containing diet in three murine bone cancer pain models.

UNLABELLED: Bone is a common metastatic site for prostate and breast cancer, and bone cancer is usually associated with severe pain. Traditional treatments for cancer pain can sometimes be ineffective or associated with side effects. Thus an increasing number of patients seek alternative therapies. In this study we investigated the analgesic effects of a soy diet on 3 experimental models of bone cancer pain. Mice were fed a diet in which the protein source was either soy or casein. After 1 week on the diet, sarcoma cells (NCTC 2472) were injected into the medullary cavity of the humeri, femur, or calcaneus. Experimenters blinded to diet of the animal assessed the pain behavior in these animals, forelimb grip force in the humerus model and paw withdrawal frequency to mechanical stimuli in the calcaneus and femur models. The effect of morphine on cancer-induced pain behavior was investigated in calcaneus and femur models. In addition, in the femur model, the effects of soy on tumor size and bone destruction were studied. The soy diet reduced secondary mechanical hyperalgesia in the femur model but had no effect on primary mechanical hyperalgesia in the calcaneus model or on movement-related hyperalgesia in the humerus model. No dietary impact was discerned in measurements of tumor size, bone destruction, and body weight in the femur model, suggesting that the soy diet had no effect on cancer growth. Morphine dose-dependently reduced hyperalgesia with no diet-based difference. These results suggest that a soy diet might provide analgesia in certain forms of hyperalgesia associated with bone cancer. PERSPECTIVE: The study raises the possibility of dietary supplements influencing aspects of cancer pain. Further research will help determine if use of nutritional supplements, such as soy proteins, can reduce opioid analgesic use in chronic pain states and help minimize the side effects associated with long term use of opioids.

Topical EMLA pre-treatment fails to decrease the pain induced by 1% topical capsaicin.

Topical capsaicin has been reported to be beneficial for the treatment of neurogenic pain. However, due to the burning pain associated with topical capsaicin, many patients discontinue treatment before therapeutic benefits are obtained. This study assessed the efficacy of EMLA (eutectic mixture of 2.5% prilocaine and 2.5% lidocaine) to block pain induced by the topical application of 1% capsaicin. Nine healthy subjects (five males and four females) participated in the study. High dose topical capsaicin (1%) was applied to a 2.5 x 2.5 cm region of both volar forearms for 6 h. One arm was pretreated (for 2 h) and cotreated with EMLA, and the other arm served as vehicle control. Average and peak pain ratings were recorded at 15-min intervals using a 0 (no pain) to 10 (worst possible pain) scale. Average and peak pain ratings were significantly lower at the EMLA site during the first 15-30 min of capsaicin treatment. However, for the remaining 5.5 h of capsaicin treatment, the pain ratings at the EMLA and vehicle sites were not significantly different. The 6 h treatment with high dose topical capsaicin (1%) produced significant desensitization to heat stimuli that was not affected by EMLA treatment. EMLA fails to produce a long lasting attenuation of the pain induced by topical application of 1% capsaicin. These results argue against the use of EMLA to block pain to topical capsaicin during the treatment of neurogenic pain.