C-fiber-Selective Peripheral Nerve Blockade

Abstract

Despite the clinical demand, current uses of local anesthetics do not allow selective blockade of nociceptive fibers. Regional anesthesia produces an analgesic effect accompanied with undesired side effects due to block of motor, non-nociceptive sensory and autonomic fibers. These side effects limit the clinical use of local anesthetics and affect the recovery and rehabilitation period after surgical procedures. Therefore one main goal of research in the field of regional anesthesia is selectively targeting nociceptive fibers. Recent studies describing the role of nociceptive specific sodium channels in generation and propagation of nociceptive signals make these channels ideal targets for pain selective blockade. In addition, novel methods of targeted delivery of charged local anesthetics selectively into nociceptors provide another potentially successful approach for c-fiber specific nerve block. This review summarizes currently on-going studies on several promising targets and methods to achieve pain selective anesthesia.

Effective Dose of Intravenous Dexmedetomidine to Prolong the Analgesic Duration of Interscalene Brachial Plexus Block

“…Presumably, the possible contributing factors for this contrasting finding might be the differences between the nerves being blocked, neuraxial versus peripheral nerves 27 ; the doses of DEX; and the volumes and types of local anesthetics used in the respective blocks where the bupivacaine is reported to produce longer motor blockade compared with ropivacaine. [28][29][30] As the dose of IV DEX increases, systemic effects such as prolonged sedation 10 and safety concerns of hemodynamic instabilities should be raised. 31 Dexmedetomidine has dose-dependent sedative effects, 24 but it usually resolves within 2 hours after terminating the infusion.…”

Large A-Fiber Activity is Required for Microglial Proliferation and P38 MAPK Activation in the Spinal Cord: Different Effects of Resiniferatoxin and Bupivacaine on Spinal Microglial Changes after Spared Nerve Injury

“…TRPV1 agonists induce desensitization and inactivation of nociceptive neurons, impeding these neurons to respond to a subsequent stimulus [ 28 ]. Recent studies have shown that activation of TRPV1 with capsaicin or lidocaine can selectivity deliver a quaternary local anesthetic QX-314 to target only nociceptive fibers for a sustained blockade [ 26 , 30 ]. However the duration of this specific blockade (<12 h) may not be long enough for the purpose of the present study.…”

“…Long-term and selective blockade of nociceptive fibers is attractive and can be achieved using the sodium channel blocker QX-314 combined with capsaicin [ 26 ] or resiniferatoxin (RTX), an ultrapotent agonist for transient receptor potential vanilloid subtype-1 (TRPV1) that is only expressed in nociceptors [ 27 , 28 ]. Nociceptive-specific block can provide analgesia without affecting motor function or pain-unrelated sensory function [ 29 , 30 ]. Recently electrical stimulation at C-fiber intensity has been shown to induce microglial changes [ 31 ], but it is unclear whether blocking nociceptive fibers alone would suppress spinal microglial activation after nerve injury.…”

Selectively targeting pain in the trigeminal system

“…One strategy is to deliver a permanently charged sodium channel blocker such as QX-314 ( N -ethyl-lidocaine) by entry through large-pore ion channels selectively expressed in nociceptive neurons [33]. The transient receptor potential vanilloid 1 (TRPV1) channel is a primary nociceptive transducer in pain-sensing neurons, activated by noxious heat (>43 °C), capsaicin, protons and endocannabinoids [8,36].…”