J Korean Neurosurg Soc.  2012 Jul;52(1):32-36. 10.3340/jkns.2012.52.1.32.

Electrophysiological and Behavioral Changes by Phosphodiesterase 4 Inhibitor in a Rat Model of Alcoholic Neuropathy

• Han KH
• Kim SH
• Jeong IC
• Lee YH
• Chang SJ
• Park BN
• Kim SW

• KMID: 2190520
• DOI: http://doi.org/10.3340/jkns.2012.52.1.32

Abstract

OBJECTIVE
Alcoholic neuropathy is characterized by allodynia (a discomfort evoked by normally innocuous stimuli), hyperalgesia (an exaggerated pain in response to painful stimuli) and spontaneous burning pain. The aim of the present study is to investigate the effect of rolipram, a phosphodiesterase 4 inhibitor, against alcohol-induced neuropathy in rats.
METHODS
Allodynia was induced by administering 35% v/v ethanol (10 g/kg; oral gavage) to Spraue-Dawley rats for 8 weeks. Rolipram and saline (vehicle) were administered intraperitoneally. Mechanical allodynia was measured by using von Frey filaments. Somatosensory evoked potential (SEP) was proposed as complementary measure to assess the integrity of nerve pathway.
RESULTS
The ethanol-induced mechanical allodynia began to manifest from 3 week, and then peaked within 1 week. Beginning from 3 week, latency significantly started to increased in control group. In rolipram treated rats, the shorter latency was sustained until 8 weeks (p<0.05). The mechanical allodynia, which began to manifest on the 3 weeks, intraperitoneal injections of rolipram sustained statistical difference until 8 weeks, the final week of the study (p<0.05).
CONCLUSION
This study suggests that rolipram might alleviate mechanical allodynia induced by alcohol in rats, which clearly has clinical implication.

Keyword

Alcoholic neuropathy; Phosphodiesterase 4 inhibitor; Rolipram

MeSH Terms

Alcoholic Neuropathy
Alcoholics
Animals
Burns
Cyclic Nucleotide Phosphodiesterases, Type 4
Ethanol
Evoked Potentials, Somatosensory
Humans
Hyperalgesia
Injections, Intraperitoneal
Rats
Rolipram
Cyclic Nucleotide Phosphodiesterases, Type 4
Ethanol
Rolipram

Figure

• 

  Fig. 1 A: A schematic illustration of the rat skull with electrode placement for SEP study. B: SEP signal at different experimental stages in the ethanol induced neuropathy control group. SEP: somatosensory evoked potential.

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  Fig. 2 The time courses of mechanical threshold in ethanol-induced neuropathy. Rolipram was intraperitoneally injected once a day. The vehicle group received equal volume of normal saline. Note that ethanol significantly decreased mechanical threshold for the first 3 weeks. Rolipram significantly ameliorated mechanical threshold decrease compared with ethanol diet and ethanol diet with vehicle injection groups (p<0.05). In this figure data are plotted as mean±standard error of the mean. Asterisks indicate values significantly different from those of ethanol diet alone and of vehicle group by using a two-way repeated measures analysis of variance with repeated time factor, followed by Tukey post hoc test.

• 

  Fig. 3 The time courses of SEP latency in ethanol-induced neuropathy. Rolipram was intraperitoneally injected once a day. The vehicle group received equal volume of normal saline. Note that ethanol significantly increased the latency of SEP from the first 3 weeks. Rolipram significantly improved increased latencies compared with ethanol diet and ethanol diet with vehicle injection groups (p<0.05). In this figure data are plotted as mean±standard error of the mean. Asterisks indicate values significantly different from those of ethanol diet alone and of vehicle group by using a two-way repeated measures analysis of variance with repeated time factor, followed by Tukey post hoc test. EP: somatosensory evoked potential.

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