Articles: hyperalgesia.
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Cysteine protease Cathepsin S (CatS) expressed by spinal microglia has been shown to play a critical role in nerve injury and inflammation-induced chronic pain. However, whether microglial CatS contributes to remifentanil-induced acute hyperalgesia remains unstudied. In the present study, intravenous remifentanil infusion induced a significant increase in the expression of premature and mature form of CatS in the activated microglia in the spinal cord. ⋯ However, increased protein level of premature form of CatS was not affected by PBN. Altogether, our findings demonstrate that neuronal ROS promote maturation of microglial CatS which facilitates activation of NMDA in the spinal dorsal horn. Therefore, such mechanism is involved in neuron-microglia positive feedback and contributes to remifentanil-induced hyperalgesia.
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Nitric oxide donors are known to produce headache in healthy as well as migraine subjects, and to induce extracephalic cutaneous hypersensitivity in rodents. However, little is known on the effect of nitric oxide donors on cephalic cutaneous sensitivity. Combining behavioral, immunohistochemical, and in vivo electrophysiological approaches, this study investigated the effect of systemic administration of the nitric oxide donor, isosorbide dinitrate (ISDN), on cephalic and extracephalic cutaneous sensitivity and on neuronal activation within the medullary dorsal horn (MDH) in the rat. ⋯ Using in vivo electrophysiological unit recordings, we show that ISDN administration never affected the spontaneous activity of trigeminal wide dynamic range neurons, but, facilitated C-fiber-evoked responses in half the neurons tested. This research demonstrates that a nitric oxide donor, isosorbide dinitrate, induces selectively cephalic hyperalgesia that arises as a consequence of central sensitization in pain pathways that subserve meningeal nociception. This model better mimics the clinical condition and offers another possibility of studying the role of nitric oxide donor in the physiopathology of headache.
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Patients with multiple sclerosis (MS) often complain of neuropathic pain. According to the Gate Control Theory of Pain, spinal networks of GABAergic inhibitory interneurons are important in modulating nociceptive inputs from the periphery. Na+-K+-2Cl- co-transporter 1 (NKCC1) and K+-Cl- co-transporter 2 (KCC2) generally dictate the tone of GABA/glycine inhibition by regulating intracellular chloride concentrations. ⋯ Treatment with bumetanide, an NKCC inhibitor, had no effect on mechanical hypersensitivity seen in mice with EAE even though it reversed the changes in the levels of NKCC1 and KCC2. We noted that bumetanide treatment, while effective at reversing the changes in monomeric KCC2 levels was ineffective at reversing the changes in oligomeric KCC2 which remained repressed. These results indicate that mechanical hypersensitivity in EAE is not mediated by altered levels of NKCC1.
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Amongst the side effects of triptans, a substantial percentage of patients experience injection site pain and tenderness, the underlying mechanism of which is unknown. We found that the dose range from 10fg to 1000ng (intradermal) of sumatriptan induced a complex dose-dependent mechanical hyperalgesia in male rats, with distinct peaks, at 1pg and 10ng, but no hyperalgesia at 1ng. In contrast, in females, there was 1 broad peak. ⋯ While selective 5-HT1D or 5-HT1B, agonists produce robust hyperalgesia in female and male rats, respectively, when co-injected the hyperalgesia induced in both sexes was attenuated. Mechanical hyperalgesia induced by sumatriptan (1pg and 10ng) is dependent on the G-protein αi subunit and protein kinase A (PKA), in IB4-positive and negative nociceptors. Understanding the mechanisms responsible for the complex dose dependence for triptan hyperalgesia may provide useful information for the design of anti-migraine drugs with improved therapeutic profiles.
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Approximately 60% to 90% of patients with borderline personality disorder (BPD) show nonsuicidal self-injurious behavior (NSSI) with cutting being the most frequently applied method. One of NSSI's functions is to reduce aversive tension. Previous studies have found a tension-reducing effect of painful tissue injury by an incision. ⋯ Our findings confirm that among BPD patients, the nociceptive input leads to stress reduction. In contrast, the impact of tissue damage on stress reduction was relatively small. In addition, the results suggest that painful stimuli lead to a greater stress reduction in BPD patients compared with HCs.