Pyrazole-based arylalkyne cathepsin S inhibitors. Part III: modification of P4 region.

Novel classes of tetrahydropyrido-pyrazole thioether amines and arylalkynes that display potency against human Cathepsin S have been previously reported. Here, key pharmacophoric elements of these two classes are merged, and SAR investigations of the P4 region are described, in conjunction with re-optimization of the P5 and P1/P1'/P3 regions. Identification of meta-substituted arylalkynes with good potency and improved solubility is described.

Dorsal root ganglion stimulation for the treatment of severe intractable pain related to obturator nerve entrapment neuropathy: A case report.

A 61-year-old Caucasian female, with severe obturator neuropathy following a left pubic ramus fracture was treated successfully with dorsal root ganglion stimulation (DRGS). Both conservative management and a dual-lead dorsal column spinal cord stimulator did not provide effective long-term results. The dorsal root ganglion (DRG) trial was completed five years following the initial fracture, resulting in 90 % pain relief. A permanent device was implanted and after one year, 90 % pain relief was still sustained. DRGS has applicability in future treatment algorithms for patients with mixed nociceptive and neuropathic groin pain refractory to conservative management.