Pain
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We investigated the scoring properties of the mouse formalin test using the time-sampling method recently developed for infant and adult rats. Formalin was injected under the plantar surface of one rear paw (10 microl, 1-8%), and pain behaviours (paw favouring, lifting and licking) and behavioural state were recorded. Correlational and regression analyses indicated that scores composed of combinations of all three pain behaviours, either summed or weighted, provided less variable indices of pain than licking alone. ⋯ Formalin dose-dependently reduced locomotion, rearing and sniffing in both the first phase and the early part of the second phase. The combination measures were sensitive to morphine (2-8 mg/kg), amphetamine (1-4 mg/kg), dipyrone (50-200 mg/kg), xylazine (0.25-1 mg/kg), and acepromazine (0.25-1 mg/kg), and resistant to diazepam (0.5-2 mg/kg), pimozide (0.05-0.25 mg/kg), pentobarbital (10 and 15 mg/kg) and indomethacin (2-8 mg/kg). Decreased pain was correlated with increased motor activity for morphine and amphetamine, and with decreased activity for xylazine and acepromazine; dipyrone and indomethacin did not alter activity levels.
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Comparative Study
Comparison of autotomy behavior induced in rats by various clinically-used neurectomy methods.
When a peripheral nerve is cut, a neuroma develops at its proximal end. Nerve-end neuromas are known to be a source of ectopic sensory input. In some humans this input may cause spontaneous and evoked neuropathic pain. ⋯ The differing scores of autotomy caused by these neurectomy methods may derive from different properties of the injury discharge produced by these methods at the time of nerve cut. Our results raise the possibility that a higher incidence of neuropathic pain or related sensory disorders in humans may be expected following cryosurgical and electrocut neurectomies. If validated by further studies, neurectomy methods eliciting lower incidence of autotomy, and sensory disorders in models not based on autotomy may produce lower levels of neuropathic pain in humans.
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The inability of opioids to control pain over time may be influenced by different factors such as drug tolerance, hyperalgesia due to repeated morphine administration or progression of the original disease. In addition, chronic pain may alter morphine tolerance development. This study examined whether chronic morphine exposure differently affects mechanical and thermal stimulus evoked pain-related behaviour in non-operated, nerve-injured and sham-operated rats. ⋯ Following morphine pretreatment, acute i.v. morphine on day 16 remained effective against both mechanical and thermal stimuli in non-operated rats, but was strongly reduced in nerve-injured rats. Sham-operated rats displayed a tendency towards a reduced effect of i.v. morphine after morphine pretreatment in the mechanical but not in the thermal test. The results suggest that mechanical afferent systems may be more sensitive to hyperalgesia associated with repetitive morphine injections than thermal systems and that nerve injury facilitates the development of tolerance to morphine analgesia.
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Randomized Controlled Trial Clinical Trial
Defining the clinically important difference in pain outcome measures.
The purpose of this study was to determine the levels of change on standard pain scales that represent clinically important differences to patients. Data from analgesic studies are often difficult to interpret because the clinical importance of the results is not obvious. Differences between groups, as summarized by a change in mean values over time, can be difficult to apply to clinical care. ⋯ This study presents data-derived cut-off points for the changes in several pain scales, each reflecting the clinically important improvement for patients treating breakthrough cancer pain episodes with OTFC. Confirmation in other patient populations and different pain syndromes will be needed. The use of consistent clinically important cut-off points as the primary outcome in future pain therapy clinical trials will enhance their validity, comparability, and clinical applicability.
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Randomized Controlled Trial Clinical Trial
Effect of pre- or post-traumatically applied i.v. lidocaine on primary and secondary hyperalgesia after experimental heat trauma in humans.
Hyperalgesia on intradermal capsaicin application can be attenuated by systemic application of local anesthetics. We tested whether low doses of local anesthetics applied pre- or post-traumatically can reduce heat trauma-induced primary and secondary hyperalgesia in humans. Six healthy volunteers consented to the randomized, double-blind, and cross-over designed study. ⋯ Thus, local anesthetics at concentrations that do not block nerve conduction substantially affect ongoing central changes in pain processing that are induced by a real tissue trauma. A significant preemptive effect could not be demonstrated. The anti-hyperalgesic effect of lidocaine is likely based on action of central (spinal) sites, but peripheral sites may also be addressed.