Articles: hyperalgesia.
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Methods Find Exp Clin Pharmacol · Oct 2010
Comparative StudyValidation of the digital pressure application measurement (PAM) device for detection of primary mechanical hyperalgesia in rat and mouse antigen-induced knee joint arthritis.
Several tests have been developed to obtain mechanical nociceptive withdrawal thresholds for arthritis-associated pain research in preclinical animal models, which are routinely used for testing the efficacy of antinociceptive pharmaceutical candidates. Here, we aimed to validate a recently introduced and commercially available digital pressure application measurement (PAM) device for the detection of primary mechanical hyperalgesia in a model of antigen-induced knee joint arthritis (AIA) in rats and mice. Two particular advantages of the PAM device are visual feedback control of the force increase rate and the detection of the complete threshold range. ⋯ Inter-observer agreement was generally higher when using PAM instead of an analog dynamometer. In conclusion, the digital PAM device is a suitable apparatus to detect primary mechanical hyperalgesia in experimental knee joint arthritis in rats and mice. The use of this device allows visual feedback control of the stimulus rate, thus minimizing the chances of confounding factors arising from differences in ramp speed.
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Spinal cord injury (SCI) is a major cause of persistent neuropathic pain of central origin. Recent evidence suggests neuropathic pain in clinically complete SCI patients correlates with limited sensory function below the lesion (sensory discomplete). On this basis we examined if the onset of mechanical hyperalgesia was different in rodents after a severe incomplete clip-compression SCI versus a complete spinal cord transection at thoracic segment T13. ⋯ Evidence of central sensitization in cervical spinal cord segments that receive sensory projections from the forelimbs was provided by immunohistochemistry for Zif268, a functional marker of neuroplasticity. Zif268-immunoreactive neurons in laminae I/II increased in response to repetitive noxious forepaw stimulation in the incomplete SCI group, and this response was reduced in the complete transection and sham-operated groups. These data are consistent with the hypothesis that neuropathic pain of cord origin is more likely to develop after SCI when there is an incomplete loss of axons traversing the lesion.
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Pituitary adenylate cyclase-activating polypeptide-38 (PACAP-38) and its receptors (PAC1 and VPAC) have been shown in the spinal dorsal horn, dorsal root ganglia and sensory nerve terminals. Data concerning the role of PACAP in central pain transmission are controversial and we have recently published its divergent peripheral effects on nociceptive processes. The aim of the present study was to investigate acute somatic and visceral nocifensive behaviours, partial sciatic nerve ligation-evoked chronic neuropathic, as well as resiniferatoxin-induced inflammatory thermal and mechanical hyperalgesia in PACAP deficient (PACAP(-/-)) mice to elucidate its overall function in pain transmission. ⋯ These data clearly demonstrate an overall excitatory role of PACAP in pain transmission originating from both exteroceptive and interoceptive areas, it is also involved in central sensitization. This can be explained by the signal transduction mechanisms of its identified receptors, both PAC1 and VPAC activation leads to neuronal excitation. In contrast, it is an inhibitory mediator at the level of the peripheral sensory nerve endings and decreases their sensitization to heat with presently unknown mechanisms.
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Protein interacting with C kinase 1 (PICK1) is a PDZ-containing protein that binds to AMPA receptor (AMPAR) GluR2 subunit and protein kinase Cα (PKCα) in the central neurons. It functions as a targeting and transport protein, presents the activated form of PKCα to synaptic GluR2, and participates in synaptic AMPAR trafficking in the nervous system. Thus, PICK1 might be involved in many physiological and pathological processes triggered via the activation of AMPARs. ⋯ Injection of CFA into a hind paw, but not a hind paw incision, increased PKCα-mediated GluR2 phosphorylation at Ser880 and GluR2 internalization in dorsal horn. These increases were absent when spinal cord PICK1 was deficient. Given that dorsal horn PKCα-mediated GluR2 phosphorylation at Ser880 and GluR2 internalization contribute to the maintenance of CFA-induced inflammatory pain, our findings suggest that spinal PICK1 may participate in the maintenance of persistent inflammatory pain, but not in incision-induced post-operative pain, through promoting PKCα-mediated GluR2 phosphorylation and internalization in dorsal horn neurons.
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Randomized Controlled Trial Clinical Trial
Predicting the analgesic effect to oxycodone by 'static' and 'dynamic' quantitative sensory testing in healthy subjects.
The large inter-individual variability in the magnitude of analgesia in response to opioids and the high prevalence of adverse events associated with their use underline the clinical importance of being able to predict who will or will not respond to opioid treatment. The present study used both static and dynamic quantitative sensory testing (QST) on 40 healthy volunteers in order to test whether this methodology can predict the analgesic effects of oral oxycodone, as compared to a placebo, on latency to onset, pain intensity, and tolerance to the cold pressor test (CPT). Static QST consisted of measuring heat and cold pain thresholds. ⋯ The static QST results showed that heat pain thresholds predicted the magnitude of reduction in pain intensity in response to oxycodone treatment (F((1,22))=5.63, p=0.027, R(2)=0.17). The dynamic QST results showed that TS predicted the effect of oxycodone on the tolerance to CPT (F((1,38))=9.11, p=0.005, R(2)=0.17). These results suggest that both static and dynamic QST have the potential to be useful in the prediction of the response to opioid treatment.