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Aim: To study the effects of intra-hippocampal injection of interleukin-2 (IL-2) on the substance P-like immunoreactivity (SP-LI) in both periaqueductal gray (PAG) and spinal cord, and on pain threshold in rats., Methods: Immunohistochemistry technique was used and the paw withdrawal threshold to radiant heat was measured., Results: Microinjection of hIL-2 480 U in hippocampus (Hip) increased the pain threshold (93% +/- 57%, P < 0.01). Injection of formaldehyde (For) in one hindpaw decreased SP-LI neuron number on both sides of PAG (2.9 +/- 2.8 vs 22.1 +/- 0.7, 12.3 +/- 2.0 vs 22.4 +/- 1.0, P < 0.01) and increased SP-LI in ipsilateral spinal cord (0.836 +/- 0.015 vs 0.59 +/- 0.09, P < 0.01). Microinjection of hIL-2 480 U in Hip inhibited the effects of For on the SP-LI on both sides of the PAG (11.3 +/- 2.3 vs 2.9 +/- 2.8, 16.9 +/- 3.4 vs 12.3 +/- 2.0, P < 0.05) and spinal cord (0.71 +/- 0.03 vs 0.836 +/- 0.015, P < 0.01). The combination of intraperitoneal injection of corticotropin and intra-hippocampal injection of IL-2 increased the number of SP-LI neurons in PAG furtherly as compared with IL-2 240 U alone (13.6 +/- 3.6 vs 7.6 +/- 4.3, P < 0.05)., Conclusion: The analgesic effects of intra-hippocampal injection of IL-2 are mediated, possibly, via the increased of SP in PAG and the decrease of SP in the spinal cord. There is a synergetic relation between IL-2 and corticotropin.

Aim: To study the effects of corticotropin (Cor) on formalin-induced hyperalgesia and the change of nitric-oxide synthase (NOS)-positive neurons in spinal dorsal horn in rats., Methods: Measurement of pain intensity rating (PIR), NADPH-d histochemistry, and Fos immunohistochemistry were adopted., Results: The increases of NOS-positive neurons, Fos, NOS/Fos double labelling neurons of the spinal dorsal horn and the PIR after formalin injection were markedly inhibited by intrathecal injecting (ith) Cor (0.5-1.5 U), which were obviously attenuated by L-arginine (Arg, 5-15 nmol, ith), the substrate of NOS., Conclusion: Cor inhibits formalin-induced hyperalgesia by the decrease of NOS-positive neurons in the spinal dorsal horn of rats.

Aim: To study the effect of corticotrophin (Cor) on somatostatin (Som) and its synthesis in spinal dorsal horn induced by formaldehyde in rats., Methods: Using double immunohistochemical stainings, and in situ hybridization., Results: Two hours after s.c. formaldehyde (5%, 200 microL) in one hindpaw of rats, the neurons of c-fos-like immunoreactivity (FLI), somatostatin-like immunoreactivity (Som-LI), Som-LI/FLI, and perprosomatostatin mRNA (PPS-mRNA) in ipsilateral spinal dorsal horn were increased obviously, as compared with the control group. The FLI and Som-LI of spinal cord were not changed by i.p. Cor. Cor (25 or 12.5 U.kg-1, i.p.) inhibited the formaldehyde-evoked FLI, Som-LI, Som-LI/FLI, and PPS-mRNA of spinal cord in a dose-dependent manner. The decrease of c-fos or Som level due to i.p. Cor in rats of chronic pain was prevented by raphe nuclei injected cyproheptadine, but not by bicuculline, naloxone, or phentolamin injected to raphe nuclei., Conclusion: The formaldehyde-evoked c-fos expression, Som, and Som synthesis of spinal cord were suppressed by Cor through the serotonin receptor of raphe nuclei.

Aim: To study the effect of corticotropin (Cor) on c-fos expression induced by formalin in spinal cord of rat and the role of receptors., Methods: Using immunohistochemistry and adrenalectomy., Results: Cor inhibited the formalin-evoked c-fos expression in rat spinal cord in a dose-dependent manner. No obvious effect was seen by i.p. Cor 10 U.kg-1, but 25 U.kg-1 reduced the evoked c-fos expression, that was blocked by phentolamine, naloxone, or verapamil, but not much changed by adrenalectomy., Conclusion: The formalin-evoked c-fos expression of rat spinal cord was suppressed by Cor through the alpha-adrenergic receptors, opiate receptors and calcium, but no relation to adrenal glands.

Aim: To observer the effect of intrathecal injection of somatostatin (Som) associated with electroacupuncture (EA) at "Jiaji" points on c-fos protein expression of spinal cord in pain rats., Methods: Rats with adjuvant arthritis were used as pain model and the c-fos-like immunoreactivity (FLI) was detected by immunohistochemistry., Results: The c-fos protein expression induced by arthritis were found in all of the I-X laminae of ipsilateral spinal cord of rats, and most of the labeled cells were located in the laminae I-II and V-VI. Som and EA suppressed the c-fos expression and the lessening of FLI cells in the spinal cord., Conclusion: Pathological pain following arthritis activated pain sensitive neurons (PSN) and evoked c-fos expression in spinal cord, Som and EA suppressed activities of these PSN, producing the effect of analgesia.

Effects of ACTH on the content of 5-HT in the hippocampus, midbrain-pons, and spinal cord and the concentration of blood glucose in rats by spectrofluorometric assay and glucose oxidase method were studied. ACTH ip 10 IU.kg-1 or 20 IU.kg-1 significantly increased the content of 5-HT in the hippocampus, midbrain-pons and spinal cord and blood glucose level, both in a dose-dependent manner; para-chloroaphetamine, p-Cpa 4 mg icv markedly reduced the 5-HT in these brain regions and spinal cord and the blood glucose level (P less than 0.01); the level of 5-HT and blood glucose were not significantly altered after icv p-Cpa+ip ACTH; adrenalectomy+ip ACTH markedly increased the 5-HT content in the brain regions and spinal cord, but the blood glucose was decreased (P less than 0.01); and 5-HT was markedly decreased by sc alloxan tetrahydrate+ip ACTH, but blood glucose did not decrease (P greater than 0.05). Thus, ACTH may influence the blood glucose level through central nervous system 5-HT, and the change of 5-HT may be related to the insulin (secretion).

Using HPLC with electrochemical detection, we found that icv somatostatin (Som) 5 or 10 micrograms increased rat's pain threshold and contents of 5-HT and 5-HIAA in hippocampus, hypothalamus and brainstem, except the 5-HIAA content of brainstem in Som 5 micrograms group. However, the changes of NE among above three areas of brain were different, the NE contents of hypothalamus and brainstem significantly increased while that of hippocampus markedly decreased. After icv Som 20 micrograms, hypoxanthine and xanthine in hippocampus and hypothalamus decreased significantly, but encephaledema occurred. Som 40 micrograms icv caused necrotic changes of neurons in brain.

The effects of ip intra-PAG injection of ACTH on serotonin (5-HT), norepinephrine (NE) contents of hippocampus and hypothalamus and pain threshold were investigated. The results showed: (1) After ip ACTH, the pain threshold, the contents of 5-HT of the two brain regions and the NE content of hippocampus were markedly elevated. Prior destruction of periaqueductal gray (PAG), the elevation of pain threshold and the increase of the 5-HT contents of two brain regions due to ip ACTH were completely abolished, while the effect of ACTH in elevating NE content of hippocampus still persisted. (2) After intra-PAG injection of ACTH, the pain threshold and the 5-HT contents in hippocampus and hypothalamus were significantly increased, however, the NE levels in hippocampus and hypothalamus showed no significant changes. The analgesic effect of the intra-PAG injection of ACTH was prevented by icv LSD, but not by naloxone, atropine, hexamethonium and phentolamine. (3) After icv ACTH, the pain threshold did not change. These results suggest that the serotoninergic system may be activated by PAG for mediation of ACTH-induced analgesia.