AAHS ASPN ASRM - 2013 Annual Meeting - American Association ...

An Alternate Nociceptive Drive: The Role of Afferent-Efferent Propioceptive System in the Maintenance of
Chronic Pain States
Institution where the work was prepared: Hand and Microsurgery Center of El Paso, El Paso, TX, USA
Jose Monsivais, MD; Hand & Microsurgery Center; Kris Robinson, PhD, FNP; University of Texas at El Paso
Neck, hip, and upper/lower limb pain often persist following adequate nerve decompression. Such symptoms are frequently dismissed or attributed to somatization
and ignored. Frequently these patients exhibit abnormal muscle activity (dystonias, spasms, etc.) not explained by other pathology. This paper is the
translation of 10 years of laboratory and clinical findings.
A relationship exists between endonerual pressure and abnormal muscle activity. Earlier research demonstrated abnormal muscle activity by EMG in the scalene
muscles followed by response of the supraspinatus, rhomboids, deltoids, ECRL, and ERCB as a result of increased endoneural pressure >40 mm/hg in median/ulnar
nerves of Nubian goats. As the pressure increased above 100 mm/hg the response was seen in the same muscles on the contralateral side. Subsequently,
this phenomenon was observed originating from the radial nerve and noted between the sciatic and tibial nerves and iliospsoas, pyriformis, and gluteus muscles
of laboratory animals and humans.
With endoneural pressure exceeding 40 mm/hg nociception originates from the ipsilateral peripheral nerve by activation of A-delta and C fibers to dorsal root
ganglia and spinal cord to the reticular formation (spinal reticular tract) and cerebellum. When pressures exceed 100 mm/hg, the afferent response crosses the
midline (spinal cord, medulla) and triggers abnormal muscle activity in homonymous muscles in the contralateral side indicating that it most likely originates
in the same spinal segment, that the propioceptive system is involved, and that the efferent activity originates at subcortical level as we have observed this to
occur under light anesthesia in humans and laboratory animals. This is one possible mechanism for the mirror image expression of pain.
In summary, a reverberating afferent-efferent loop is activated that starts with peripheral receptors (transduction) travels along the spinal cord (transmission)
to the midbrain (modulation), cerebellum or sensory cortex (perception) with a motor activity (response). However, prolonged efferent activation generates muscle
damage through persistent muscle contraction which in turn induces afferent nociceptive impulses by activation of propioceptive receptors and dorsal horn
sensitization. This response induces further muscle activity which triggers further nociception and response. Once this point is reached and the somatic-gamma
propioceptive loop closes, nerve decompression may not be sufficient to resolve the pain state. We suggest that this cascading and chronic response induces
activity that maintains pain and, at this point, is independent of endoneural pressure. Thus, the propioceptive system becomes a nocioceptive drive.
Effect of Levetiracetam and Morphine in an Animal Model of Neuroma Pain
Institution where the work was prepared: Johns Hopkins, Baltimore, MD, USA
Lun Chen; Richard Meyer; Michael Dorsi; Allan J. Belzberg, MD; Johns Hopkins University
An injury to a peripheral nerve may lead to the development of a neuroma where mechanical stimulation of the neuroma leads to painful paresthesias. The
antinociceptive effect of antiepileptic drugs have been reported in neuropathic pain syndromes. In this study we compared the effect of levetiracetam to that
of morphine on reducing the pain behavior associated with mechanical stimulation of a neuroma in the rat tibial neuroma transposition (TNT) model.
Methods:
In male Sprague-Dawley rats (250-300g), the left tibial nerve was exposed, tightly ligated with 6-0 silk, and cut just proximal to the division of the medial and
lateral plantar nerves. A subcutaneous tunnel was created to a location 1-3 mm superior to the lateral malleolus. The tibial nerve stump was passed through
the tunnel to the lateral site. A blinded experimenter applied a 150 mN von Frey filament to the ligature site (visible through skin). A score is assigned based
on the frequency of paw withdrawal to five applications of the von Frey probe. In addition, graded von Frey filaments were applied to the sites on the lateral
surface of the hindpaw corresponding to the sural nerve territory. Paw withdrawal thresholds to mechanical stimuli were obtained at these sites. Animals
received a systemic administration (i.p.) of levetiracetam (20, 40, 100, 200, 400 mg/kg), morphine (0.5, 1, 2, 4, 8 mg/kg), or vehicle in a blinded, random fashion.
Behavioral testing was performed before surgery, day 6 postoperative, and then on drug delivery days 9 and 15 postoperative. A given animal was tested
with one dose of each drug (with at least a two day wash out period). Each dose was tested on eight animals.
Results:
Mechanical stimulation to the skin overlying the neuroma with the von Frey probe provoked a rapid withdraal of the hindpaw in 96% of the animals, 6 days
after neuroma surgery. Hyperalgesia to mechanical stimuli applied to the sural nerve distribution was demonstrated in 86% of animals 6 days after surgery.
These behaviors were not affected by the systemic administration of vehicle or levetiracetam. In contrast, administration of morphine led to a dose-dependent
decrease in the frequency of paw withdrawal to mechanical stimulation of the neuroma and increase in paw withdrawal threshold to stimulation of the paw.
Conclusion:
These results indicate that levetiracetam, in contrast to morphine, does not induce an antihyperalgesic effect in the TNT model of neuroma pain.
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