Our report shows that the sciatic nerve block with bupivicaine and clonidine, initiated approximately 3 years after amputation, produced modest short-term relief. The pulsed radiofrequency treatment resulted in long-term relief of phantom limb pain. The patient was able to wean herself off all oral medications and has been pain free for 4 months.

The binding properties of seven CD4-blocking monoclonal antibodies raised against recombinant gpl20 of human immunodeficiency virus type 1 strain MN (HWV-lMN) and two CD4-blocking monoclonal antibodies to recombinant envelope glycoproteins gpl20 and gpl60 of substrain IIIB of HIVLm were analyzed. With a panel of recombinant gpl20s from seven diverse HIV-1 isolates, eight of the nine antibodies were found to be strain specific and one was broadly cross-reactive. Epitope mapping revealed that all nine antibodies bound to epitopes located in the fourth conserved domain (C4) of gpl20. Within this region, three distinct epitopes could be identified: two were polymorphic between HIV-1 strains, and one was highly conserved. Studies with synthetic peptides demonstrated that the conserved epitope, recognized by antibody 13H8, was located between residues 431 and 439. Site-directed mutagenesis of gpl20 demonstrated that residue 429 and/or 432 was critical for the binding of the seven antibodies to gpl20 from HIV-lMN. Similarly, residues 423 and 429 were essential for the binding of monoclonal antibody 5C2 raised against gpl20 from HIV-1111B. The amino acids located at positions 423 and 429 were found to vary between strains of HIV-1 as well as between molecular clones derived from the MN and LAI isolates of HIV-1. Polymorphism at these positions prevented the binding of virus-neutralizing monoclonal antibodies and raised the possibility that HIV-1 neutralization serotypes may be defined on the basis of C4 domain sequences. Analysis of the binding characteristics of the CD4-blocking antibodies demonstrated that their virus-neutralizing activity was directly proportional to their gpl20-binding affinity. These studies account for the strain specificity of antibodies to the C4 domain of gpl20 and demonstrate for the first time that antibodies to this region can be as effective as those directed to the principal * Corresponding author.

BackgroundEvaluation of analgesics in large animals is a necessary step in the development of better pain medications or gene therapy prior to clinical trials. However, chronic neuropathic pain models in large animals are limited. To address this deficiency, we developed a neuropathic pain model in sheep, which shares many anatomical similarities in spine dimensions and cerebrospinal fluid volume as humans.MethodsA neuropathic pain state was induced in sheep by tight ligation and axotomy of the common peroneal nerve. The analgesic effect of intrathecal (IT) morphine was investigated. Interspecies comparison was conducted by analyzing the ceiling doses of IT morphine for humans, sheep, and rats.ResultsPeroneal nerve injury (PNI) produced an 86% decrease in von-Frey filament-evoked withdrawal threshold on postsurgery day 3 and the decrease lasted for the 8-week test period. Compared to the pre-injury, sham, and contralateral hindlimb, the IT morphine dose that produces 50% of maximum analgesia (ED50) for injured PNI hindlimb was 1.8-fold larger and Emax, the dose that produces maximal analgesia, was 6.1-fold lower. The sheep model closely predicts human IT morphine ceiling dose by allometric scaling. This is in contrast to the approximately 10-fold lower morphine ceiling dose predicted by the rat spinal nerve ligated or spared nerve injury models.ConclusionPNI sheep model has a fast onset and shows stable and long-lasting pain behavioral characteristics. Since the antinociceptive properties of IT morphine are similar to those observed in humans, the PNI sheep model will be a useful tool for the development of analgesics. Its large size and consistent chronic pain behavior will facilitate the development and evaluation of surgical intervention and gene therapy. The PNI sheep pain model provides us with the opportunity for multi-species testing, which will improve the success of clinical trials.

The management of chronic pain can be very challenging. Often, physicians employ intrathecal (IT) drug delivery systems as a last resort to relieve intractable pain. The system consists of an implantable pump that stores and delivers medication through a catheter to the IT space. Programmability is achieved by positioning an external devise over the implanted pump to change the mode of drug delivery. The innovations in programmable IT drug delivery systems are expanding more rapidly than ever before. Unfortunately, the rapid expansion is accompanied by a lack of prospective randomized trials examining these new options. In an effort to improve results and reduce side effects, publications by experts or expert consensus panels provide guidance for the community. The purpose of this article is to provide a summary of high interest topics in recent publications.

Trigeminal neuralgia (TN) is a chronic condition affecting the fifth cranial nerve and resulting in sporadic intense burning and shock-like pain lasting for seconds to minutes that can be incapacitating to patients. Atypical TN includes additional features such as continuous pain and sensory disturbances in the area innervated by one or more branches of the trigeminal nerve. Documented cases of TN have dated back to the 18th century. Today, there are roughly 140,000 people suffering with this condition in the U.S.A. Conventional treatments for this disorder include medical management with nonconvulsants such as carbamazepine, which decrease the nerves response to peripheral stimulation. These agents have good initial pain relief, but relief rates fall off dramatically over the long-term. Recently, methadone has shown promise as a pharmacologic adjunct to patients with intractable neuropathic noncancer pain, including patients suffering from TN. Cases refractory to medical management can be treated with surgical microdecompression or minimally invasive procedures such as radiofrequency (RF) treatment. Pulsed RF (PRF) is a method gaining interest as it is delivered in pulses, allowing adequate time for dissipation of heat and energy resulting in less damage to surrounding structures. This case report describes the successful treatment of atypical V2 TN refractive to medical management requiring PRF treatment, a sphenopalatine block series, and low-dose methadone.