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Plantar Test

Days from Bennett surgery

Mechanical stimulus

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Peripheral injury can give rise to cortical reorganization. Partial peripheral nerve injuries are used as animal models for human chronic pain states, because such animals exhibit pain-like behavior. In this study we examine the relationship between behavioral changes following chronic constriction injury (CCI) and the concurrent cortical reorganization, by monitoring the temporal evolution of these parameters in animals equipped with telemetric recordings.

From acute to chronic pain state: telemetric electrophysiology mapping plasticity of

somatosensory cortex in chronic constriction injury rats H.H. Berra, S. Lavarello, M. Baliki, D.R. Chialvo, A.V. Apkarian

Department of Physiology, Feinberg Medical School, Northwestern University, Chicago, IL, 60611, USA.

SFN 2003New

Orleans 813.14

S u p p o r t e d b y S u p p o r t e d b y NIH NINDS NS42660NIH NINDS NS42660

1. We observe distinct evoked potentials for mechanical and thermal stimuli.

2. The evoked potentials change in time following unilateral CCI.

3. The changes in evoked potentials are not causally related to the observed mechanical and thermal threshold changes.

4. Anesthesia independent component of the tested behavior is spinally mediated.

5. Therefore, the cortical reorganization does not reflect the tested behavior. This suggests that spinal reflexive behaviors measured in CCI are not related to the induced cortical plasticity.

Group averaged (n=11) electrical stimulation contralateral evoked potentials (cEP) show a peak around 15 msec for forepaw and 20 msec for hind paw stimulation (corresponds to ~ 10 m/s conduction velocity). The cEP amplitude for CCI paw decreases in 4 days, and recovers in 20 days; while for the non-injured hind paw cEP decreased only after 30 days (p<0.05). No significant changes are seen for forepaw cEPs.

One month after CCI, under anesthesia withdrawal latencies were longer, and the non-injured side shows more responses. Therefore, spinal excitability seems higher on uninjured side, after one month (n = # of animals).

For the injured paw, initially (7 days) EPe decrease in amplitude with no change in mechanical thresholds, later (30 days) EPe partially recover while mechanical thresholds are decreased. For the non-injured paw, threshold decreases late after injury (30 days) together with decreases in EPe.

INTRODUCTION

In freely moving Sprague-Dawley rats with implanted transmitters (Data-Science Instruments) we monitor the effects of chronic constriction nerve injury (CCI, Bennett & Xie, 1988), to relate pain behavior and brain cortical electrophysiology. Animals are implanted with bilateral parietal (RP, LP) and unilateral right prefrontal (RF) electrodes (n = 23 animals monitored over 5 weeks).

Pain behavioral testing: Animals are studied behaviorally from 1 week prior to 4 weeks post surgery. Sensitivity to mechanical as well as thermal responses are examined. Mechanical responses are quantified using Von Frey hairs induced response threshold forces. Thermal responses are quantified by withdrawal latencies to different intensity infra-red stimuli, on the Plantar Test.

Evoked potentials: Thermal stimulus related evoked potentials (EPt) are collected at different time-points relative to the peripheral induction of CCI. Also large fiber mediated electrical evoked potentials (EPe) are recorded, under anesthesia.

METHODS

Mechanical thresholds are constant up to 10 days, and decrease bilaterally by day 30 after unilateral CCI injury. Thermal paw withdrawal latencies, for infrared (IR) intensities (30 & 70), show the same temporal evolution as the mechanical responses (p<0.05 at 30 days; n=23 animals for all measures).

RESULTS

SUMMARY & CONCLUSIONS

Mechanical & Thermal

responses

Comparing EPt amplitudes before injury to 7 days after CCI, we observe preserved EPt in contralateral parietal cortex from the CCI hind paw, and its disappearance everywhere else including from stimulation of non-injured hind paw (p<0.05). EPt is average for ~ 40 trials in 23 animals.

Thermal IR stimuli (70 A.U.) give rise to a well defined EPt peaking around 65 msecs. The EPt is seen in both parietal cortices (RP & LP), and peak in the frontal cortex (RF) as a negative peak. Responses are similar for stimulating either hind paw.

Mechanical thresholds vs.electrical evoked potentials7

Before CCI + 7 days +30 days injured paw non-injured paw

50 % threshold (gr)

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Large fiber mediated

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one animal example

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6Changes in EPt after CCI injury

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3Anesthesia effects

Plantar Test (IR-70 A.U.)

* p<3.46E-07 **p<3.75E-04

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