Differential nerve block

An anatomic circumstance that sometimes creates exceptions to the above rules for differential nerve block is the location of the fibers within the peripheral nerve bundle. In large nerve trunks, fibers located circumferentially are the first to be exposed to the local anesthetic when it is administered into the tissue surrounding the nerve. In the extremities, proximal sensory fibers are located in the outer portion of the nerve trunk, whereas the distal sensory innervation is located in the central core of the nerve. Thus, during infiltration block of a large nerve, sensory analgesia first develops proximally and then spreads distally as the drug penetrates deeper into the core of the nerve. 

The clinical importance of a differential nerve block is that certain sensory modalities may be blocked without the loss of motor function. Fortuitously, the most susceptible modality is pain because analgesia is usually the desired effect. If the dosage and administration of the anesthetic is optimal, it will produce analgesia without any significant loss of skeletal muscle function. This fact may be advantageous if motor function is required, such as during labor and delivery.14 If... 

Wildsmith JAW, Brown DT, Paul D, Johnson S. Structure-activity relationships in differential nerve block at high and low frequency stimulation. Br J Anaesth 1989 63 444-452. 

Jaffe RA, Rowe MA. Differential nerve block direct measurements on individual myelinated and unmyelinated dorsal root axons. Anesthesiology 1996 84 1455-1464. 

Sakai T, Tomiyasu S, Yamada H, et al. Quantitative and selective evaluation of differential sensory nerve block after transdermal lidocaine. Anesth Analg. 2004 98 248-251. 

The interruption, interference, or blockade of painful stimuli has been used in the management of pain for several decades. Acute, chronic, and post-operative pain can be diminished with various types of regional anesthesia or specific nerve blocks. In the setting of chronic pain management, various peripheral nerve blocks can be diagnostic, prognostic, or therapeutic in nature. Nerve blocks are generally most useful when a specific nerve or limb is affected. Neural blockade may help differentiate a peripheral source of pain from a... 

Butterworth J, Ririe DG, Thompson RB, et al. Differential onset of median nerve block randomized, double-blind comparison of mepivacaine and bupivacaine in healthy volunteers. Br JAnaesth 1998 81 515-521. 

However, these results contradict long-accepted in vitro studies on mammalian peripheral nerve fiber axon diameter. These studies suggest that larger myelinated A fibers which conduct with higher velocity may be more susceptible to peripheral nerve blockade with local anesthetics than smaller unmyehnated C fibers which conduct more slowly [12,13]. Jaffe and Rowe in 1996 [14] actually found no difference in sensitivity to lidocaine based on axon diameter. Many mechanisms in addition to axon diameter have been proposed for lidocaine s differential neural blockade, such as differences in Na channel block (state-de-pendent vs. frequency-dependent) between different nerve fiber types. Further research is needed to elucidate the underlying mechanism as well as the discrepancy between the differential blockade witnessed in epidural and peripheral nerve blocks. 

Peripheral nerve functions are not affected equally by local anesthetics. Loss of sympathetic function usually is followed by loss of temperature sensation sensation to pinprick, touch, and deep pressure and last, motor function. This phenomenon is called differential blockade. Differential blockade is the result of a number of factors, including the size of the nerve, the presence and amount of myelin, and the location of particular fibers within a nerve bundle. For conduction to be effectively blocked, the local anesthetic must exert its effects over the distance between several nodes of Ranvier. Since the smallest nerves (C fibers) have no myelin, they can be most easily blocked thus, sympathetic functions often are blocked soon after a local anesthetic is applied to a particular nerve bundle. Small myelinated nerves have correspondingly short distances between nodes of Ranvier and therefore are often blocked next. These nerves subserve temperature and sharp pain sensation. Larger nerves then become blocked, accounting for the loss of function up to and including motor innervation. 

Nerves differ in their sensitivity to local anaesthetics. When lidocaine (lignocaine) is applied to a mixed peripheral nerve the onset of the block is in the order, vasodilatation (B fibres), loss of pain and temperature (C and A6 fibres), muscle spindle reflex (Ay fibres), motor and pressure (A(3 fibres) and large motor and proprioception (Aa fibres). This phenomenon is called differential block. There are other minor variations in this ranking order among the local anaesthetics. The basis of differential block is thought to be the result of variability in the sensitivity of different nerves to the same agent. 

In contrast to the functional information available for the roles of ACh and AChE, the function or functions of RBC and serum ChEs are still matters for speculation. One idea is that they protect the body from natural anti-ChE agents (e.g., phyosos-tigmine) encountered during the evolution of the species another idea is that they have specific but still unknown roles in tissues. For example, there are reports that inhibition of BuChE activity blocks adhesion of neurites from nerve cells in culture and that AChE promotes outgrowth of neurites as if the enzymes had roles in cell adhesion and differentiation. 

Ml nerve fibres are sensitive to local anaesthetics but. in general, small-diameter fibres are more seitsitivc than large fibres. Thus, a differential block can be achieved where the smaller pain and autonomic fibres are blocked, while coaise touch and movement libres are spared. Local anaesthetics vary widely in Ihcir potency. duiaiiun of action, toxicity and ability to penetrate mucous membranes. 

Many strains of Clostridium botulinum synthesize an exoenzyme (C3) which catalyzes the specific ADP-ribosylation of a 21 kUodalton substrate (1). AH C3-producing strains also make either Cl or D neurotoxins. Botulinal neurotoxins block the release of neurotransmitters from nerve terminals and at the start of our work the Cl and D neurotoxins had been reported to be ADP-ribosyl transferases (2, 3). Hence we decided to determine if there was any relationship between C3-catalyzed ADP-ribosylation and nemosecretion. Here we show that when C3 is introduced into die cytosol of PC12 cells it induces a morphological differentiation but does not alter secretion of a neurotransmitter. By contrast the introduction of a neurotoxin into the cytosol of PC 12 cells does block secretion but causes no shape change. 

Ease of use, tolerability, opioid sparing. Bupivacaine provides chnically useful differential block particularly when dilute infusions are employed. It is associated with frequency-dependent blockade whereby noxious nerve fibers that conduct action potentials most frequently are first to be blocked, while larger-caliber less active sensory motor fibers are relatively spared. The rapid injection of a large volume of bupi-... 

Lidocaine s differential blockade has been examined with peripheral and neuraxial administration [ 10-11 ]. Peripheral nerve libers seem to respond differently to lidocaine than dorsal nerve roots. Epidural lidocaine seems to block small unmyelinated C fibers (supplying temperature sensation) more effectively than 281 larger myelinated A fibers (A-beta supplying touch. 

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