ziconotide and Nociceptive-Pain

Intrathecal drug delivery represents an advanced modality for refractory chronic pain patients as well as intractable spasticity. This article reviews the advantages and indications for intrathecal therapy, as well as recommendations for proper patient selection using a multidisciplinary team to provide a global assessment of the impact of chronic pain on the patient's well-being. The goals and expectations of trialing are discussed alongside advantages and disadvantages of several trialing techniques. A discussion of outcomes is presented for patients with chronic pain due to both malignant and nonmalignant causes.

Topics: Analgesics, Non-Narcotic; Analgesics, Opioid; Chronic Pain; Humans; Infusion Pumps, Implantable; Infusions, Spinal; Morphine; Neuralgia; Nociceptive Pain; omega-Conotoxins; Pain; Patient Selection; Spinal Cord; Treatment Outcome

A hallmark of rheumatoid arthritis (RA) is the chronic pain that accompanies inflammation and joint deformation. Patients with RA rate pain relief as the highest priority; however, few studies have addressed the efficacy and safety of therapies directed specifically toward pain pathways. The ω-conotoxin MVIIA (ziconotide) is used in humans to alleviate persistent pain syndromes, because it specifically blocks the voltage-gated calcium 2.2 (CaV 2.2) channel, which mediates the release of neurotransmitters and proinflammatory mediators from peripheral nociceptor nerve terminals. The aims of this study were to investigate whether blockade of CaV 2.2 can suppress arthritis pain, and to examine the progression of induced arthritis during persistent CaV 2.2 blockade.. Transgenic mice expressing a membrane-tethered form of MVIIA under the control of a nociceptor-specific gene (MVIIA-transgenic mice) were used in the experiments. The mice were subjected to unilateral induction of joint inflammation using a combination of antigen and collagen.. CaV 2.2 blockade mediated by tethered MVIIA effectively suppressed arthritis-induced pain; however, in contrast to their wild-type littermates, which ultimately regained use of their injured joint as inflammation subsided, MVIIA-transgenic mice showed continued inflammation, with up-regulation of the osteoclast activator RANKL and concomitant joint and bone destruction.. Taken together, our results indicate that alleviation of peripheral pain by blockade of CaV 2.2- mediated calcium influx and signaling in nociceptor sensory neurons impairs recovery from induced arthritis and point to the potentially devastating effects of using CaV 2.2 channel blockers as analgesics during inflammation.

Topics: Animals; Arthritis, Experimental; Arthritis, Rheumatoid; Calcium Channel Blockers; Calcium Channels, N-Type; Disease Models, Animal; Mice; Mice, Transgenic; Nociceptive Pain; Nociceptors; omega-Conotoxins; RANK Ligand; Stifle; Tumor Necrosis Factor-alpha; Up-Regulation