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Several isoforms of neuronal nitric oxide synthase (nNOS) have been identified. Antisense approaches have been developed which can selectively down-regulate nNOS-1, which corresponds to the full-length nNOS originally cloned from the brain, and nNOS-2, a truncated form lacking two exons which is generated by alternative splicing, as demonstrated by decreases in mRNA levels. Antisense treatment also lowers nNOS enzymatic activity. Downregulation of nNOS-1 prevents the development of morphine tolerance. Whereas morphine analgesia is lost in control and mismatch-treated mice given daily morphine injections for 5 days, mice treated with antisense probes targeting nNOS-1 show no decrease in their morphine sensitivity over the same time period. Conversely, an antisense probe selectively targeting nNOS-2 blocks morphine analgesia, shifting the morphine dose-response curve over 2-fold to the right. Both systems are active at the spinal and the supraspinal levels. An antisense targeting inducible NOS is inactive. Studies with N G -nitro-L-arginine, which does not distinguish among NOS isoforms, indicate that the facilitating nNOS-2 system predominates at the spinal level while the inhibitory nNOS-1 system is the major supraspinal nNOS system. Thus, antisense mapping distinguishes at the functional level two isoforms of nNOS with opposing actions on morphine actions. The ability to selectively down-regulate splice variants opens many areas in the study of nNOS and other proteins.

Transperineal 125iodine implants of the prostate can be performed with ultrasound guidance, a simple technique that has met with widespread acceptance. However, ultrasound does not allow good visualization of the pubic bones in relation to the pelvic outlet, and the pubic bones may interfere with needle placement in the anterior peripheral aspect of the prostate. Adequate irradiation of the entire periphery of the prostate is important to assure tumor control, since most tumors are multicentric and may involve the anterior aspect of the prostate. A computerized tomography-based treatment planning procedure that allows for angulation of transperineal needles to avoid the pubic bones and still reaches the most peripheral aspects of the gland is described. The technique also allows for the use of transrectal ultrasound and fluoroscopy to verify correct needle placement in the prostate at the procedure. Early treatment results, based on prostate specific antigen and regression of palpable tumors, are encouraging.

Cancer pain assessment and management are integral to palliative medicine. This paper reviews recent publications in the period 1999-2004 in the broad categories of epidemiology, pain assessment, nonpharmacologic approaches to cancer pain (radiation therapy, anesthetic blocks, palliative surgery and chemotherapy, complementary and alternative medicine), and in nociceptive pain, neuropathic pain, visceral pain, and bone pain.

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Cancer pain often presents in a body region. This review summarizes articles from 1999-2004 relevant to cancer pain syndromes in the head and neck, chest, back, abdomen, pelvis, and limbs. Although the evidence is limited, progress is being made in further development of the evidence base to support and guide current practice.

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