Pain
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Peripheral neural mechanisms underlying the sensations of irritation, discomfort, and itch accompanying the eye allergic response have not been hitherto analyzed. We explored this question recording the changes in the electrical activity of corneoconjunctival sensory nerve fibers of the guinea pig after an ocular allergic challenge. Sensitization was produced by i.p. ovalbumin followed by repeated application in the eye of 10% ovalbumin on days 14 to 18. ⋯ Only capsazepine attenuated tearing rate increase and sensitization of the polymodal nociceptors response to CO2. Capsazepine also prevented the decrease in cold thermoreceptor activity caused by the allergic challenge. We conclude that changes in nerve impulse activity accompanying the ocular allergic response, primarily mediated by activation of nociceptor's TRPV1 and to a lesser degree by activation of TRPA1 channels, explain the eye discomfort sensations accompanying allergic episodes.
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Many of the widely used anticancer drugs induce dose-limiting peripheral neuropathies that undermine their therapeutic efficacy. Animal models of chemotherapy-induced painful peripheral neuropathy (CIPN) evoked by a variety of drug classes, including taxanes, vinca alkaloids, platinum-complexes, and proteasome-inhibitors, suggest that the common underlying mechanism in the development of these neuropathies is mitotoxicity in primary nerve sensory axons (PNSAs) arising from reduced mitochondrial bioenergetics [eg adenosine triphosphate (ATP) production deficits due to compromised respiratory complex I and II activity]. The causative mechanisms of this mitotoxicity remain poorly defined. ⋯ Our findings reveal that the development of mechano-hypersensitivity induced by paclitaxel, oxaliplatin, and bortezomib was prevented by administration of the peroxynitrite decomposition catalyst Mn(III) 5,10,15,20-tetrakis(N-n-hexylpyridinium-2-yl)porphyrin (MnTE-2-PyP(5+)) without interfering with their anti-tumor effects. Peak CIPN was associated with the nitration and inactivation of superoxide dismutase in the mitochondria, but not in the cytosol, as well as a significant decrease in ATP production within the PNSAs; all of these events were attenuated by MnTE-2-PyP(5+). Our results provide continued support for the role of mitotoxicity in the development of CIPN across chemotherapeutic drug classes, and identify peroxynitrite as a key mediator in these processes, thereby providing the rationale towards development of "peroxynitrite-targeted" therapeutics for CIPN.
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Randomized Controlled Trial
Limb-specific autonomic dysfunction in complex regional pain syndrome modulated by wearing prism glasses.
In unilateral upper-limb complex regional pain syndrome (CRPS), the temperature of the hands is modulated by where the arms are located relative to the body midline. We hypothesized that this effect depends on the perceived location of the hands, not on their actual location, nor on their anatomical alignment. In 2 separate cross-sectional randomized experiments, 10 (6 female) unilateral CRPS patients wore prism glasses that laterally shifted the visual field by 20°. ⋯ When prism glasses made the healthy hand appear to be on the affected side of the body midline, even though it was not, the healthy hand cooled down (Δ°C=-0.30 ± 0.15°C). Friedman's analysis of variance and Wilcoxon pairs tests upheld the results (P<0.01 for all). We conclude that, in CRPS, cortical mechanisms responsible for encoding the perceived location of the limbs in space modulate the temperature of the hands.
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Randomized Controlled Trial
A pain model with a neuropathic somatosensory lesion: Morton neuroma.
A randomized, double-blind, three-period cross-over study was performed to characterize the sensory phenotype and pain demographics in patients with Morton neuroma (n=27) and to explore the effects of local administration (2mL) of placebo and lidocaine (1 and 10mg/mL) around the neuroma. Using the pain quality assessment scale (PQAS), the highest rating was seen for unpleasant pain and intensity of deep pain and the lowest for sensitive skin. Ongoing pain was reported in 32% of patients. ⋯ Following placebo treatment, pain after step-ups was similar in patients with and without hyperalgesia, indicating that the presence of hyperalgesia does not affect the pain intensity evoked by step-ups or walking. This pain model in patients with Morton neuroma allows investigation of drugs in a cross-over design and provides an opportunity to explore drug effects on both pain and QST variables. Commonly, neuromas are surgically removed and can be characterized in depth in vitro, thereby allowing close links to be established between pathophysiology and drug effect.