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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One of the most commonly used experimental animal models for neuropathic pain is the chronic constriction injury (CCI) where four loose ligatures are tied around the sciatic nerve. One disadvantage of this model is the introduction of foreign material into the wound, which causes a local inflammatory reaction. Thus the distinction between the neuropathic and the inflammatory component of pain is difficult in this model. ⋯ In the epineurium the number of macrophages was strikingly increased after CCI compared with PST, indicating that the response of the immune system is different in a structural lesion with and without foreign material. In conclusion, PST is a pure nerve injury model without an epineurial inflammatory component due to foreign material and is therefore well suited for studying the role of local endoneurial processes in the development and maintenance of neuropathic pain. Also, the importance of regeneration in the termination of hyperalgesia can convincingly be shown in this model.
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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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Case Reports
Patterns of spread in complex regional pain syndrome, type I (reflex sympathetic dystrophy).
There are reports that complex regional pain syndrome, type I (reflex sympathetic dystrophy; CRPS-I/RSD) can spread from the initial site of presentation, but there are no detailed descriptions of the pattern(s) of such spread. We describe a retrospective analysis of 27 CRPS-I/RSD patients who experienced a significant spread of pain. Three patterns of spread were identified. 'Contiguous spread (CS)' was noted in all 27 cases and was characterized by a gradual and significant enlargement of the area affected initially. 'Independent spread (IS)' was noted in 19 patients (70%) and was characterized by the appearance of CRPS-I in a location that was distant and non-contiguous with the initial site (e.g. ⋯ In some it may be due to a local spread of pathology (CS); in others it may be a consequence of a generalized susceptibility (IS). In the MS case, spread may be due to abnormal neural functioning spreading via commissural pathways. Alternatively, we discuss the possibility that all three kinds of spread may be due to aberrant CNS regulation of neurogenic inflammation.
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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.