Orphanin FQ/nociceptin (OFQ/N) and its receptor share substantial structural features and cellular actions with classic opioid peptides and receptors, but have distinct pharmacological profiles and behavioral effects. Currently there is an active debate about whether OFQ/N produces hyperalgesia or analgesia. Using a well-defined brainstem pain-modulating circuit, we show that OFQ/N can cause either an apparent hyperalgesia by antagonizing mu opioid-induced analgesia or a net analgesic effect by reducing the hyperalgesia during opioid abstinence. It presumably produces these two opposite actions by inhibiting two distinct groups of neurons whose activation mediates the two effects of opioid administration. OFQ/N antagonism of the hyperalgesia may have significance for the treatment of opioid withdrawal and sensitized pain.
Antiepileptics used for treating neuropathic pain have various actions including voltage-gated Na+ and Ca2+ channels, glutamate-receptor inhibition, and GABAA-receptor activation, while local anesthetics are also used to alleviate the pain. It has not been fully examined yet how nerve conduction inhibitions by local anesthetics differ in extent from those by antiepileptics. Fast-conducting compound action potentials (CAPs) were recorded from frog sciatic nerve fibers by using the air-gap method. Antiepileptics (lamotrigine and carbamazepine) concentration dependently reduced the peak amplitude of the CAP (IC50 = 0.44 and 0.50 mM, resp.). Carbamazepine analog oxcarbazepine exhibited an inhibition smaller than that of carbamazepine. Antiepileptic phenytoin (0.1 mM) reduced CAP amplitude by 15%. On the other hand, other antiepileptics (gabapentin, sodium valproate, and topiramate) at 10 mM had no effect on CAPs. The CAPs were inhibited by local anesthetic levobupivacaine (IC50 = 0.23 mM). These results indicate that there is a difference in the extent of nerve conduction inhibition among antiepileptics and that some antiepileptics inhibit nerve conduction with an efficacy similar to that of levobupivacaine or to those of other local anesthetics (lidocaine, ropivacaine, and cocaine) as reported previously. This may serve to know a contribution of nerve conduction inhibition in the antinociception by antiepileptics.
Primary palmar hyperhidrosis (PPH) is a unique disorder of unknown cause. It is characterized by excessive perspiration of the eccrine sweat gland in the palm, sole, and the axilla. It is presumed that PPH results from overactivation of the cholinergic sympathetic nerve or dysfunction of the autonomic nervous system. There have been no genetic studies on the disease. We performed a linkage analysis of 11 families including 42 affected and 40 unaffected members using genome-wide DNA polymorphic markers to identify the disease locus. Diagnosis of their PPH was made by direct inspection, interviewing and measurement of the sweating rate with perspirometer. Consequently, from data of three of the 11 families examined, the combined maximum two-point LOD scores of 3.08 and 3.16 (recombination fraction = 0) were obtained at the D14S283 and D14S264 loci, respectively, on chromosome 14q11.2-q13, under an assumption that two liability conditions depend on age. These regions were ruled out in eight other families. Haplotype analysis of the three families supported that one of the PPH locus is assigned at minimum to about a 6-cM interval between D14S1070 and D14S990 and at maximum to about a 30-cM interval between D14S1070 and D14S70. This is the first report of systemic mapping of the PPH locus.
The offending artery was the PICA in most cases. MVD is expected to be very effective, especially when the radiological images show the following 3 findings: 1) high-origin PICA, 2) the PICA making an upward loop, and 3) the PICA coursing the supraolivary fossette. The transcondylar fossa approach is suitable for transposing the PICA by the stitched sling retraction technique, and provides sufficient surgical results.
Purpose
When performing endoscopic thoracic sympathectomy (ETS) in palmar hyperhidrosis patients, a device can be used to measure sweat volume pre- and postoperatively in order to assess indications and treatment effects. In this study, we measured changes in the dynamics of sweating in hyperhidrosis patients pre- and postoperatively and compared the values with those in healthy subjects without hyperhidrosis.
Methods
The patient group comprised 25 persons with palmar hyperhidrosis who were scheduled for ETS. The dynamics of sweating was measured at 1 day prior to surgery and at 2 days postoperatively, in 18 patients at > 1 year postoperatively in another palmar hyperhidrosis group, and in 20 healthy subjects without hyperhidrosis. A device for measuring local sweat volume was applied at the thenar eminence of both palms. Indicators established were basal sweat rate (BSR; mg/min/cm2), peak sweat rate (PSR; mg/min/cm2) during mental stress (sympathetic sweating response), sweat volume (SV), and sweat time (ST; s).
Results
After surgery, all of the indicators were significantly reduced in hyperhidrosis patients and there was very little response to mental stress. The subgroup of these patients assessed at > 1 year after ETS showed a trend of increased BSR similar to that of healthy subjects. These changes did not correlate with the extent of the removal surgery. Preoperatively, hyperhidrosis patients had significantly greater BSR, PSR, and SV and longer ST than healthy subjects.
Conclusion
All of the sweating parameters were increased in palmar hyperhidrosis patients prior to surgery. Immediately after ETS, all these parameters were significantly reduced. At > 1 year after ETS, the BSR had increased to a level similar to that of the healthy volunteers, although PSR did not respond to mental stress.
The present study tested the hypothesis that endogenous opioid peptides acting at the delta-opioid receptor (DOR) in the rostral ventromedial medulla (RVM) contribute to the antinociception elicited by the mu-opioid receptor (MOR) agonist DAMGO in the midbrain periaqueductal gray (PAG). Following microinjection of DAMGO into the PAG, either the highly selective DOR antagonist TIPP[psi] or the DOR2 antagonist naltriben (NTB) was microinjected into the RVM. Both TIPP[psi] (1.0 microg) and NTB (5.0 ng) significantly attenuated the analgesic effect of PAG DAMGO but had no effect when given before PAG saline. These results confirm and extend previous studies suggesting that PAG mu-opioids activate a descending system with a DOR mediated endogenous opioid link in the RVM.
Introduction: Mirogabalin, which is a selective ligand of the a 2 d subunit of voltage-gated Ca 2? channels, was recently approved in Japan for peripheral neuropathic pain. The a 2 d ligands, including mirogabalin and pregabalin, are associated with significant risk of adverse events (AEs) such as somnolence or dizziness, leading to poor compliance and subsequent inefficacy. Safety and efficacy data for switching patients from pregabalin to mirogabalin are scarce. Methods: This prospective, single-arm, openlabel study involving ten participating centers in Japan recruited patients aged C 20 years with peripheral neuropathic pain [visual analog scale (VAS) score C 40 mm]. Where necessary, patients underwent a 1-week tapering period to reduce their pregabalin dose, after which
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