title: Effect of intrathecal octreotide on thermal hyperalgesia and evoked spinal c-Fos expression in rats with sciatic constriction injury.
abstract: This study was designed to determine whether intrathecal octreotide (sandostatin), a synthetic octapeptide derivative of somatostatin, relieved thermal hyperalgesia and reduced the evoked spinal c-Fos expression in rats with chronic constriction injury (CCI) of the sciatic nerve. Intrathecal catheters were implanted in rats 7 days before CCI of the sciatic nerve over the left hind limb. After confirmation of the development of thermal hyperalgesia by decreased paw withdrawal latencies (PWL) to heat stimulation 7 days after CCI, intrathecal sandostatin at 20, 40, and 80 microg was administered, respectively. Rats in the control group received saline injections intrathecally. PWLs were evaluated at 30, 60, 120, 180, and 240 min after drug administration. Detection of Fos-like immunoreactivity (Fos-LI) neurons in the dorsal horn of the spinal cord following drug administration was performed after mechanical stimulation (stroking of the hind paws) on the 14th day after CCI. The reduction of PWL was attenuated significantly in the groups that received intrathecal sandostatin at 20, 40, and 80 g when compared with the saline group. However, PWL did not return to pre-CCI values in all groups. In the 40 microg group, PWL returned up to 76% of pre-CCI values 120 min after drug administration. Stroking of the hind paw in CCI-treated (ipsilateral) limbs induced a significantly greater expression of spinal Fos-LI neurons than that of non-CCI treated (contralateral) limbs in each group. The number of Fos-LI neurons in animals receiving intrathecal sandostatin was dose-dependently reduced. Expression of Fos-LI neurons in the 80 microg group was nearly completely inhibited. These data suggest that intrathecal sandostatin significantly relieved thermal hyperalgesia behaviorally but with limited effects and dose-dependently reduced spinal Fos-LI neurons expression evoked by stroking stimulation, which may reflect mechanical allodynia in rats with sciatic constriction injury. This implies that intrathecal sandostatin was effective in the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesiology, National Cheng Kung University Medical Center, 138 Sheng-Li Road, Tainan 704, Taiwan Department of Anesthesiology, Chi-Mei Medical Center, Tainan, Taiwan Department of Neurosurgery, National Cheng Kung University Medical Center, 138 Sheng-Li Road, Tainan 704, Taiwan Department of Anatomy, National Cheng Kung University Medical Center, 138 Sheng-Li Road, Tainan 704, Taiwan.
authors.forename: Yu-Chuan
authors.initials: YC
authors.lastname: Tsai
authors.forename: Edmund C
authors.initials: EC
authors.lastname: So
authors.forename: Hsing-Hong
authors.initials: HH
authors.lastname: Chen
authors.forename: Li-Kai
authors.initials: LK
authors.lastname: Wang
authors.forename: Chi-Hsien
authors.initials: CH
authors.lastname: Chien
mesh_terms: D000818:Animals; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D006930:Hyperalgesia / Q000188:drug therapy* / Q000378:metabolism; D007278:Injections, Spinal; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015282:Octreotide / Q000008:administration & dosage*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000188:drug therapy* / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D016760:Proto-Oncogene Proteins c-fos; D015282:Octreotide