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.