Articles: hyperalgesia.
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Arthritis and rheumatism · Feb 2004
Evidence of augmented central pain processing in idiopathic chronic low back pain.
For many individuals with chronic low back pain (CLBP), there is no identifiable cause. In other idiopathic chronic pain conditions, sensory testing and functional magnetic resonance imaging (fMRI) have identified the occurrence of generalized increased pain sensitivity, hyperalgesia, and altered brain processing, suggesting central augmentation of pain processing in such conditions. We compared the results of both of these methods as applied to patients with idiopathic CLBP (n = 11), patients with widespread pain (fibromyalgia; n = 16), and healthy control subjects (n = 11). ⋯ At equal levels of pressure, patients with CLBP or fibromyalgia experienced significantly more pain and showed more extensive, common patterns of neuronal activation in pain-related cortical areas. When stimuli that elicited equally painful responses were applied (requiring significantly lower pressure in both patient groups as compared with the control group), neuronal activations were similar among the 3 groups. These findings are consistent with the occurrence of augmented central pain processing in patients with idiopathic CLBP.
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Previous studies in our laboratory have shown that long-term (a period of weeks) increases in pain-related behavior were correlated with the activation of spinal microglia after subcutaneous injection of formalin into the dorsal surface of 1 hind paw. The present study examined whether intrathecal delivery of suramin (a P2 receptor antagonist) blocks microglia activation and long-term hyperalgesia induced by formalin injection. Suramin was administered by using an osmotic pump attached to an intrathecal catheter. Suramin delivery (1.25 microg/kg/h) began 1 day before the formalin injection and lasted for 4 days. Rats were observed by using a modified hot plate test before and at different times after formalin injection. The spinal cord was surveyed for changes in microglia labeling as shown by OX-42 staining at different times after formalin injection. Suramin decreased both the hyperalgesic sensitivity to the thermal stimuli and microglial activation induced by formalin injection as compared to the saline-treated group. This suggests that adenosine triphosphate is one potential mediator that activates spinal cord microglia and enhances pain-related behavior in the formalin model. ⋯ This report suggests that blocking specific spinal P2 receptors might decrease the central enhancement of pain caused by peripheral injury and inflammation. One mechanism might be by blocking the activation of spinal microglia. Thus, P2 antagonists might have therapeutic usefulness in certain pain conditions.
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Anesthesia and analgesia · Feb 2004
Randomized Controlled Trial Clinical TrialThe effects of remifentanil and gabapentin on hyperalgesia in a new extended inflammatory skin pain model in healthy volunteers.
We tested the responsiveness of measures of hyperalgesia in a model of UVB-induced inflammatory hyperalgesia with remifentanil, gabapentin, and the combination of both drugs in a double-blinded, active placebo-controlled, 4-way-crossover design in 16 volunteers. A circular skin area was irradiated with UVB-light 20 h before the application of gabapentin (600 mg) and 2 h later remifentanil (0.08 microg.kg(-1).min(-1), 40 min). In the sunburn spots we observed stable decreases of the heat pain perception thresholds (HPPT, mean difference, 4.45 degrees C; 95% confidence interval [CI], 3.32 degrees -5.59 degrees ) and heat pain tolerance thresholds (HPTT; mean difference, 5.43 degrees C; 95% CI, 4.50 degrees -6.35 degrees ) compared with normal skin. Further, large areas of mechanical hyperalgesia to pinprick adjacent to the erythema spots developed in all subjects. Overall remifentanil increased the HPPT (mean increase, 2.47 degrees C; 95% CI, 1.86 degrees -3.09 degrees, P < 0.001) and HPTT (mean increase, 3.18 degrees C; 95% CI, 2.65 degrees -3.71 degrees, P < 0.001) and reduced the area of secondary hyperalgesia by 59% (mean decrease, 5326 mm(2); 95% CI, 4233-6419 mm(2), P < 0.001) compared with placebo. In the sunburn remifentanil markedly increased the HPTT by 86% compared with normal skin (additional increase, 2.57 degrees C; 95% CI, 1.71 degrees -3.43 degrees). This different effect was not seen in the HPPT. With the exception of a small increase of HPTT in the sunburn (P = 0.02) gabapentin had no noticeable effect on either hyperalgesia. In conclusion, opioid analgesia was reliably demonstrated in this new extended pain model. ⋯ Opioid analgesia was reliably demonstrated in a new inflammatory model of primary and secondary hyperalgesia. Gabapentin showed no antihyperalgesic and no opioid-enhancing effect in this model.
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This article reports the development of a new hind limb pain model in which an incisional stab wound is placed on the front and back of the calf, causing both superficial and deep tissue injury. The injury causes primary mechanical hyperalgesia on the calf and secondary hind paw hyperalgesia, which served as the focus of the present study. Animals with unilateral stab wounds showed a significant increase in percent paw withdrawal (secondary mechanical hyperalgesia, reversed by morphine administration) from 2 to 48 hours after surgery, but no evidence of thermal hyperalgesia. In contrast, animals with bilateral leg injuries showed bilateral secondary mechanical and thermal hyperalgesia. Rats with unilateral leg incisional stab wounds showed a significant decrease in cage activity in both the horizontal and vertical directions, monitored by using a novel activity box approach, as compared to their 24-hour baseline levels or to the activity of naïve animals. Analysis of spinal cord Fos labeling demonstrated that calf injury significantly increased Fos expression in laminae I to VI of the L3-L5 cord segments. The data indicate that this model might be useful for evaluation of the mechanisms underlying penetrating injury-induced primary and secondary hyperalgesia or for testing the effect of analgesics on hyperalgesia induced by such injury. ⋯ Stab wounds and other types of penetrating wounds routinely encountered in emergency rooms and clinics are accompanied by pain associated with superficial and deep tissue injury. Here we present a rodent stab wound model that affords an opportunity to study the mechanisms of pain associated with traumatic injury.
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Review
Neuroimmune activation and neuroinflammation in chronic pain and opioid tolerance/hyperalgesia.
One area that has emerged as a promising therapeutic target for the treatment and prevention of chronic pain and opioid tolerance/hyperalgesia is the modulation of the central nervous system (CNS) immunological response that ensues following injury or opioid administration. Broadly defined, central neuroimmune activation involves the activation of cells that interface with the peripheral nervous system and blood. ⋯ CNS innate immunity and Toll-like receptors, in particular, may be vital players in this orchestrated immune response and may hold the answers to what initiates this complex cascade. The challenge remains in the careful perturbation of injury/opioid-induced neuroimmune activation to down-regulate this process without inhibiting beneficial CNS autoimmunity that subserves neuronal protection following injury.