Acute and chronic sectioning of fifth lumbar spinal nerve has equivalent effects on the primary afferents of sciatic nerve in rat spinal cord

Research presented here sought to determine if opioid induced tolerance is linked to activity changes within the PI3Kγ-AKT-cGMP-JNK intracellular signaling pathway in spinal cord or peripheral nervous systems. Morphine or saline injections were given subcutaneously twice a day for five days (15 mg/kg) to male C57Bl/6 mice. A separate cohort of mice received spinal nerve ligation (SNL) one week prior to the start of morphine tolerance. Afterwards, spinal cord, dorsal root ganglia, and sciatic nerves were isolated for quantifying total and phosphorylated- JNK levels, cGMP, and gene expression analysis of Pik3cg, Akt1, Pten, and nNos1. This pathway was downregulated in the spinal cord with increased expression in the sciatic nerve of morphine tolerant and morphine tolerant mice after SNL. We also observed a significant increase in phosphorylated- JNK levels in the sciatic nerve of morphine tolerant mice with SNL. Pharmacological inhibition of PI3K or JNK, using thalidomide, quercetin, or SP600125, attenuated the development of morphine tolerance in mice with SNL as measured by thermal paw withdrawal. Overall, the PI3K/AKT intracellular signaling pathway is a potential target for reducing the development of morphine tolerance in the peripheral nervous system. Continued research into this pathway will contribute to the development of new analgesic drug therapies.

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Effects of systemic administration of ciliary neurotrophic factor on Bax and Bcl-2 proteins in the lumbar spinal cord of neonatal rats after sciatic nerve transection

Brazilian Journal of Medical and Biological Research ◽

10.1590/s0100-879x2008005000052 ◽

2008 ◽

Vol 41 (11) ◽

pp. 1024-1028 ◽

Cited By ~ 12

Author(s):

A.C.S. Rezende ◽

A.S. Vieira ◽

F. Rogério ◽

L.F. Rezende ◽

A.C. Boschero ◽

...

Keyword(s):

Spinal Cord ◽

Sciatic Nerve ◽

Neurotrophic Factor ◽

Ciliary Neurotrophic Factor ◽

Systemic Administration ◽

Lumbar Spinal Cord ◽

Nerve Transection ◽

Neonatal Rats ◽

Sciatic Nerve Transection ◽

Lumbar Spinal

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Regional blood flow in transected rat spinal cord during hypothermia

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1990.259.6.h1649 ◽

1990 ◽

Vol 259 (6) ◽

pp. H1649-H1654

Author(s):

T. Sakamoto ◽

A. Iwai ◽

W. W. Monafo

Keyword(s):

Spinal Cord ◽

Blood Flow ◽

Sciatic Nerve ◽

Rectal Temperature ◽

Regional Blood Flow ◽

Spinal Cord Transection ◽

The Other ◽

Rat Spinal Cord ◽

Caudal Spinal Cord

Regional blood flow (RBF) increases in the spinal cord and sciatic nerve of acutely hypothermic rats. To determine whether cord transection affects this response, we measured RBF in rat spinal cord and sciatic nerve 2 h after cord transection at vertebrae T8 (n = 18 rats) and T11 (n = 18 rats) using [14C]butanol distribution. Nine in each group were normothermic controls. In T11 transection-hypothermia (25-27 degrees C rectal temperature), RBF increased in the three rostral cord segments by 28-40% (P less than 0.05); caudally, cord RBF was depressed in two segments (P less than 0.05), unchanged in the other; RBF fell in nerve (P less than 0.05). In T8 transection-hypothermia, RBF was unchanged in the two rostral cord segments; caudally, RBF was depressed in one cord segment (P less than 0.05) and unchanged in the others; RBF was unchanged in nerve. We conclude that RBF does not rise in caudal spinal cord segments or in sciatic nerve during hypothermia in rats with prior spinal cord transection.

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