Articles: hyperalgesia.
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Clinical Trial
Opioid tolerance and hyperalgesia in chronic pain patients after one month of oral morphine therapy: a preliminary prospective study.
There is accumulating evidence that opioid therapy might not only be associated with the development of tolerance but also with an increased sensitivity to pain, a condition referred to as opioid-induced hyperalgesia (OIH). However, there are no prospective studies documenting the development of opioid tolerance or OIH in patients with chronic pain. This preliminary study in 6 patients with chronic low back pain prospectively evaluated the development of tolerance and OIH. Patients were assessed before and 1 month after initiating oral morphine therapy. The cold pressor test and experimental heat pain were used to measure pain sensitivity before and during a target-controlled infusion with the short-acting mu opioid agonist remifentanil. In the cold pressor test, all patients became hyperalgesic as well as tolerant after 1 month of oral morphine therapy. In a model of heat pain, patients exhibited no hyperalgesia, although tolerance could not be evaluated. These results provide the first prospective evidence for the development of analgesic tolerance and OIH by using experimental pain in patients with chronic back pain. This study also validated methodology for prospectively studying these phenomena in larger populations of pain patients. ⋯ Experimental evidence suggests that opioid tolerance and opioid-induced hyperalgesia might limit the clinical utility of opioids in controlling chronic pain. This study validates a pharmacologic approach to study these phenomena prospectively in chronic pain patients and suggests that both conditions do occur within 1 month of initiating opioid therapy.
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Glutamate is a primary excitatory neurotransmitter in the mammalian CNS. Glutamate released from presynaptic neurons is cleared from the synaptic cleft passively by diffusion and actively by glutamate transporters. In this study, the role of glutamate transporters in sensory processing in the spinal cord has been investigated in behavioral, in vivo and in vitro experiments. ⋯ Whole cell recordings made from superficial dorsal horn neurons in an isolated whole spinal cord from newborn rats (2-3 weeks old) revealed that bath-applied L-trans-pyrrolidine-2,4-dicarboxylic acid (100 microM) produced partial membrane depolarization, increased spontaneous action potentials with decreased neuronal membrane resistance and time constant, but without significant changes of capacitance. Finally, the amplitude and duration of primary afferent evoked-excitatory postsynaptic currents recorded from neurons in the substantia gelatinosa in the spinal slices from young adult rats (6-8 weeks old) were increased in the presence of L-trans-pyrrolidine-2,4-dicarboxylic acid (100 microM). This study indicates that glutamate transporters regulate baseline excitability and responses of dorsal horn neurons to peripheral stimulation, and suggests that dysfunction of glutamate transporters may contribute to certain types of pathological pain.
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Acta Anaesthesiol Belg · Jan 2006
Randomized Controlled Trial Comparative StudyThe use of intraoperative epidural or spinal analgesia modulates postoperative hyperalgesia and reduces residual pain after major abdominal surgery.
The use of intraoperative multimodal analgesia has clearly improved postoperative pain control, mortality and morbidity after major surgical procedures. However, very few clinical trials have studied the longterm impact of intraoperative epidural or spinal analgesia on chronic postsurgical pain (CPSP) development. Even less studies have evaluated the modulatory effect of intraoperative neuraxial analgesia on objective changes (i.e. mechanical hyperalgesia) reflecting central sensitization. ⋯ An effective intraoperative neuraxial block of nociceptive inputs from the wound using multimodal analgesia--specifically when involving spinal analgesics and antihyperalgesic drugs--contributes to prevent central sensitization and hence reduces CPSP after major abdominal procedures.
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Devices designed for mechanical pain threshold studies are often difficult to implement. The purpose of this study was to investigate a simple tool based on calibrated forceps to induce quantifiable mechanical stimulation in the rat on a linear scale. The most suitable protocol was tested by determining the effects of 3 repetitive measurements on both hind paws, respectively, during long-term (9 days), mid-term (1 day), and short-term (2 hours). Only threshold increase related to weight gain over long-term was observed, suggesting that moderate rat training can be used. The capacity of the device to reveal hyperalgesia was tested in a model of carrageenan-induced inflammation in the hind paw. The hyperalgesia was maximal 6 hours after carrageenan injection and progressively decreased. Similar, although more variable, responses were observed with von Frey filaments. Morphine-induced analgesia resulted in a dose-dependent increase of paw threshold. Tolerance to morphine administrated on a once daily schedule (10 mg/kg) during 5 days was revealed by a significant decrease in analgesia by day 3. Taken together, these results demonstrated accuracy of this device for easy, fast, and reproducible measure of mechanical pain threshold on rat limbs. Moreover, it allows the performance of rat testing with minimal constraint, which reduces data variability. ⋯ The calibrated forceps is an easy to use device well-suited to rapidly test mechanical pain threshold with accuracy. It is well-designed for preclinical behavioral screening of noxious or analgesic properties of molecules.
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Administration of the neurotrophin nerve growth factor (NGF) to rats and humans has been shown to induce both thermal and mechanical hyperalgesia and is used as a model of inflammatory pain. Here we describe a mouse model of secondary hyperalgesia after NGF application. NGF was injected into the biceps femoris muscle unilaterally, and at various intervals afterwards the electromyographic (EMG) activity from the same muscle was recorded in response to mechanical von Frey hair stimulation of the plantar surface of the hind paw in isoflurane-anesthetized mice. Secondary cutaneous hyperalgesia in the hind paw reached a peak 60 minutes after injection and returned to baseline levels after an additional 60 minutes. This was followed by a second increase in EMG magnitude at 24 hours after injection that was still present after 5 days. The effects of NGF were dose-dependent, and a dose of 2 microg/g NGF had the maximal observed effect. No increase in EMG magnitude occurred on the untreated side. This study describes a quantitative mouse model of prolonged secondary cutaneous hyperalgesia after NGF-induced muscle inflammation that can be used for genetic manipulations of putative central molecular pathways that underlie secondary hyperalgesia. ⋯ This study describes the development of a novel model of NGF-induced secondary hyperalgesia. The development of this model will allow further investigations into the processes that underlie the development of secondary hyperalgesia and pain associated with the musculature.