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 25-28 September, 2018 | Singapore
and improving lymphatic and capillary drainage from the region of the triad.
Axon The most effective way to interfere with electrical signaling is to interfere with sodium channels, so here we see the return of the local anesthetics.
When used along a major axon use of local anesthetics is generally termed ‘regional anesthesia’ and this is clearly a hallmark of food animal practice. However,
a huge resurgence has occurred across all types
of human and veterinary species with fantastic new applications. The advantage to targeting the axon with local anesthetics is that it avoids placing drug right at
the site of the injury. Both the biology of injured tissue (acidic, edematous, etc) and the pharmacology of the local anesthetics (pH sensitive, anti-inflammatory, painful on injection, nerve damage with repeated administration) provide interactions that are avoided by placing drug remote to the injury. A disadvantage to using a local anesthetic along the axon is that, although the signal
is blocked from entering the dorsal horn, the activity continues and the peripheral site of injury. Therefore the release of inflammatory mediators, the uptake of these mediators into the bloodstream and passing of the signal to the DRG still occurs. Therefore the interference into the pain processing is not as complete as once thought when a regional technique is used. Some of the exciting advances in regional techniques have come about through improved accuracy of drug placement. Nerve stimulation and/or ultrasound are fantastic methods for verifying needle placement. An excellent review by Luis Campoy titled: Fundamentals of Regional Anesthesia using Nerve Stimulation in the Dog can be found on
Photobiomodulation (low level laser therapy) plays an important role at the axonal level. Pain signaling has been shown to decrease with photodynamic therapy, and one of the proposed mechanisms is disruption of axonal flow due to disruption of flow along the filaments within axons. Furthermore, cytochrome c activity is amplified, which provides a pro-metabolic, immune modulatory effect.
Likewise, using sound for biomodulation with shock wave therapy has been shown to improve tissue healing and reduce pain in tendon, bone and skin injuries.
Cell Body (in the DRG) Therapies directed at the cell body generally fall into the chronic pain category. Increased expression of a variety of ion channels and receptors accompany chronic pain states. Opioid receptors are synthesized, packaged and sent to peripheral locations. Sodium channel sub-types are slowly switched to tetrodo-toxin resistant types (not- responsive to traditional sodium channel blockers). Likewise, calcium channels are upregulated and different sub-types emerge. Cyclo-oxygenase subtypes increase
(COX 2 specifically) in the cell body and terminals.
Therefore, the cell body in the DRG is an important target for transcriptionally directed therapies. NSAIDs play some of their pain-relieving role here and both
the centrally acting and peripherally acting NSAIDS probably have some access to the DRG. Steroids work in this location both by interfering with COX and also by causing transcriptional changes. Acetaminophen serves a COX 3 modifying role in the DRG and dorsal horn, although it does not serve as an anti-inflammatory in peripheral tissues.
Anti-epileptic drugs often target high-use receptor subtypes of sodium and calcium channels. Drugs such as Phenytoin, Carbemazepin, Zoneisamide and Lamotrigene target high-use sodium channels. Gabapentin and Pregablin target calcium channel expression.
Although most of the cell body therapies are directed
at chronic changes, it has recently been recognized that the cell body is highly involved in the effect of low-concentration systemic lidocaine administered via constant rate infusion (Lidocaine CRI). While this method has become increasing popular due to analgesia and pro-motility effects on the gastro-intestinal system,
the mechanism of action has been unclear as it has been shown that the doses are too low to justify a blocking effect on peripheral tissues, and the drug is excluded from the central nervous system by the blood- brain barrier. Meclizine is an orally-available sodium channel blocker of the same class as lidocaine and
can sometimes be useful in pain states that respond to lidocaine infusions.
Dorsal Horn An entire graduate course can be filled
with treatments directed at decreasing pain signaling through the dorsal horn. We have already discussed descending inhibition from activation of non-pain sensory fibers sending competitive signals through lamina 1-5
in the axon section. We have discussed several of the transcriptionally mediated changes to ion channels above in the cell body section. The bulk of the cell body discussion plays out in the dorsal horn, which is, after all, an extension from the cell body.
Glutamate and substance P are major players in synaptic conductance; however, their roles are too diverse throughout the body to serve as good specific targets for pain therapy. The major receptors for glutamate are AMPA, NMDA and metabotropic glutamate receptors. The NMDA receptor tends to remain quiescent in
the dorsal horn (it is much more active in the brain
as it serves an important role in learning). It becomes activated only when enough activity passes through the synapse to dislodge a Mg ion that occupies the pore. However, ‘sustained activity’ to a nerve is really only 10-15 minutes or less, once again pointing out

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