Articles: hyperalgesia.
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Herpesvirus-mediated transfer of the human preproenkephalin gene to primary afferent nociceptors prevents phasic thermal allodynia/hyperalgesia in mice. It is not known, however, whether similar viral treatments would reverse ongoing or chronic pain and allodynia/hyperalgesia. To this end, mice were given intrathecal injections of pertussis toxin (PTX), which produces a weeks-long thermal hyperalgesia apparently by uncoupling certain G proteins from inhibitory neurotransmitter receptors. ⋯ Interestingly, however, while the anti-hyperalgesic effect of the enkephalin-encoding virus on C-fiber-mediated responses was reversed by intrathecal application of micro or delta opioid antagonists, only delta antagonists reversed the effect of this virus on Adelta hyperalgesia. Thus, virus-mediated delivery of the proenkephalin cDNA reverses thermal hyperalgesia produced by PTX-induced ribosylation of inhibitory G proteins by an opioid-mediated mechanism. These results suggest that herpesvirus vectors encoding analgesic peptides may be useful in attenuating centrally mediated, ongoing neuropathic pain and/or hyperalgesia.
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We hypothesized that glutamate (Glu) released from the peripheral terminals of primary afferents contributes to the generation of mechanical hyperalgesia following peripheral nerve injury. Nerve injury was performed on rats with a lumbar 5 spinal nerve lesion (L5 SNL), which was preceded by L5 dorsal rhizotomy (L5 DR) to avoid the potential central effects induced by L5 SNL through the L5 dorsal root. Mechanical hyperalgesia, as evidenced by a reduction in paw withdrawal threshold (PWT), was short-lasting (<6 days) after L5 DR, but persistent (>42 days) after L5 SNL preceded by L5 DR. ⋯ However, this onset was not affected by alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate receptor antagonist 2,3-dioxo-6-nitro-1,2,3,4,-tetrahydrobenzo[f]quinoxaline-7-sulfonamide (NBQX; 100 nmol). When the same injection was given after L5 SNL-induced mechanical hyperalgesia had been established, MK-801 reversed the PWT reduction for 30-75 min, whereas NBQX, DL-AP3, or APDC had no effect. These results suggest that the manipulation of the peripheral Glu receptors reduces neuropathic pain, by blocking NMDA and group-I mGlu receptors and by stimulating group-II mGlu receptor during the induction phase of neuropathic pain, but only by blocking the NMDA receptor during its maintenance phase.
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Anesthesia and analgesia · Jan 2004
Amiodarone decreases heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain.
Lidocaine is effective in controlling ventricular dysrhythmia and neuropathic pain. Amiodarone, like lidocaine, has sodium channel blocking properties. In the present study we explore whether amiodarone has a similar effect as lidocaine on the heat, cold, and mechanical hyperalgesia seen in the rat model of neuropathic pain. Ten male Sprague-Dawley rats were anesthetized. Four loose ligatures were placed on the sciatic nerve of the right hindpaw. A sham operation was performed on the contralateral hindpaw (control). Heat hyperalgesia was determined by comparing each paw withdrawal latency to heat stimulation (radiant heat source, 50 degrees C). Cold hyperalgesia was assessed with acetone application. Mechanical hyperalgesia was determined by comparing the mechanical threshold in the ligated and control hind paws using calibrated von Frey filaments. Amiodarone was intraperitoneally administered at doses of 1, 5, 10, 20, 50, and 100 mg/kg after the development of hyperalgesia. The animals were tested for hyperalgesia before and 1, 3, and 24 h after the administration of a single dose of amiodarone. Intrathecal catheters were implanted in 5 new rats, and amiodarone 5 mg/kg was injected. Testing for heat, mechanical, and cold hyperalgesia was performed similarly in the intrathecal amiodarone administration group. Amiodarone produces statistically significant decreases of heat, cold, and mechanical hyperalgesia after intraperitoneal administration. Results are statistically significant at 10 mg/kg (heat hyperalgesia), 20 mg/kg (mechanical hyperalgesia), and 100 mg/kg (cold hyperalgesia) intraperitoneally. Hyperalgesia returns 24 h after a dose. The intrathecal administration of amiodarone produces a nonstatistically significant reduction of hyperalgesia. Amiodarone seems to have a similar effect as lidocaine on the hyperalgesia seen in the rat model of neuropathic pain. As the half-life of amiodarone is significantly longer that that of lidocaine (mean, 53 days versus 90 min) in humans, it may have the potential to provide a longer lasting (and perhaps more effective) effect than lidocaine on neuropathic pain states. ⋯ Amiodarone was found to produce a statistically significant decrease in heat, cold, and mechanical hyperalgesia in a rat model of neuropathic pain after intraperitoneal injection. Considering its long half-life in humans, amiodarone has the potential to provide long lasting pain relief in neuropathic pain states.
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Experimental neurology · Jan 2004
Cyclooxygenase inhibition in nerve-injury- and TNF-induced hyperalgesia in the rat.
After nerve injury, cyclooxygenase-2 (COX-2) is upregulated in spinal cord and peripheral nerve, the latter being dependent on tumor necrosis factor-alpha (TNF). Here we asked whether COX inhibitors attenuate pain behavior induced by chronic constrictive sciatic nerve injury (CCI) or intraneural injection of TNF (2.5 pg/ml). Rats received either 0.9% saline, the nonselective COX inhibitor ibuprofen (40 mg/kg) or the selective COX-2 inhibitor celecoxib (10 or 30 mg/kg) twice daily by gavage started 2 days before, 12 h or 7 days after surgery. ⋯ In spinal cord, no change in PGE2 levels was observed. In contrast to the marked inhibition of nerve-injury-induced upregulation of PGE2 by COX inhibitors, the effect on pain behavior was modest. Nerve-injury- and TNF-induced pain-related behavior seem to be only partly dependent on peripheral prostaglandins.
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J. Invest. Dermatol. · Jan 2004
Ultraviolet radiation-induced inflammation as a model for cutaneous hyperalgesia.
The effects of UVA-I and solar simulated radiation on skin sensitivity to thermal and mechanical stimuli were compared in normal volunteers. Individual minimal erythema doses (MED) for each source were determined and previously unexposed buttock skin was exposed to 1, 2 and 3 MED of each spectrum. Erythema, and mechanical and thermal pain thresholds were quantified from 3 to 72 hours post-irradiation. ⋯ These data demonstrate the usefulness of UVR-induced inflammation as a model of cutaneous hypersensitivity. This model has clinical relevance for the study of hyperalgesia in general and the abnormal sensitivity of sunburnt skin in particular. It is likely to be useful in the assessment of peripherally acting analgesic drugs.