The gamma
isoform of
protein kinase C (PKCgamma) is an injury-activated intracellular modulator that boosts neuronal activity in algesic and neuroregenerative signalling pathways.
Acetyl-L-carnitine (
ALCAR), a physiological compound with role in bioenergetic functions, shows an antihyperalgesic effect and at the same time can exert neuroregenerative and
neuroprotective effects. Aimed to explore the link between
pain and neuroregeneration, the effect of
ALCAR treatment (100 mg kg(-1) i.p. twice daily for 15 days) on PKCgamma and
mitogen-activated protein kinases (MAPKs) expression has been evaluated in CCI (chronic constriction injury) rats. The sciatic nerve and the lumbar tract of the spinal cord were processed to evaluate the levels of the phosphorylated form of PKCgamma, ERK 1,2, SAP/JNK, p-38 and c-Jun; furthermore, the
mRNA expression of the early genes c-Jun and c-Fos has been investigated. Fifteen days after injury, the analysis in the sciatic nerves highlighted a bilateral increase of the activated forms of PKCgamma, ERK 1,2 and SAP/JNK, whereas c-Jun showed an increase only ipsilaterally.
ALCAR completely prevented
mechanical hyperalgesia and provoked in the nerve a c-Jun increment only. In the lumbar tract of the spinal cord, higher levels of activated PKCgamma, ERK 1,2, p38, SAP/JNK and
c-Jun proteins were detected in the ipsilateral side in respect of
sham.
ALCAR was able to stimulate this expression profile. At the transcriptional level c-Jun
mRNA was increased in the ipsilateral side of spinal cord of CCI saline-treated rats, whereas c-Fos
mRNA was unchanged.
ALCAR had a stimulatory effect on both these early genes. These findings may represent a different approach in the study of the complex balance between
pain and neuroregeneration and could constitute the basis for developing new disease modifying agents in the treatment of
neuropathic pain.