Bao-Cheng Lin

Only through the brain nuclei, arginine vasopressin regulates antinociception in the rat

The effect of arginine vasopressin (AVP) on rat antinociception was investigated. Intraventricular injection of 50 or 100 ng AVP dose-dependently increased the pain threshold; in contrast, intraventricular injection of 10 microl anti-AVP serum decreased the pain threshold; both intrathecal injection of 200 ng AVP or 10 microl anti-AVP serum and intravenous injection of 5 microg AVP or 200 microl anti-AVP serum did not influence the pain threshold. Pain stimulation reduced AVP concentration in hypothalamic paraventricular nucleus (PVN), and elevated AVP concentration in hypothalamic supraoptical nucleus (SON) and periaqueductal gray (PAG), but no change in AVP concentration was detected in pituitary, spinal cord and serum. The results indicated that AVP regulation of antinociception was limited to the brain nuclei.

Arginine vasopressin induces periaqueductal gray release of enkephalin and endorphin relating to pain modulation in the rat

Previous study has proven that microinjection of arginine vasopressin (AVP) into periaqueductal gray (PAG) raises the pain threshold, in which the antinociceptive effect of AVP can be reversed by PAG pretreatment with V2 rather than V1 or opiate receptor antagonist. The present work investigated the AVP effect on endogenous opiate peptides, oxytocin (OXT) and classical neurotransmitters in the rat PAG. The results showed that AVP elevated the concentrations of leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek) and beta-endorphin (beta-Ep), but did not change the concentrations of dynorphinA(1-13) (DynA(1-13)), OXT, classical neurotransmitters including achetylcholine (Ach), choline (Ch), serotonin (5-HT), gamma-aminobutyric acid (GABA), glutamate (Glu), dopamine (DA), norepinephrine (NE) and epinephrine (E), and their metabolic products in PAG perfusion liquid. Pain stimulation increased the concentrations of AVP, L-EK, M-Ek, beta-Ep, 5-HT and 5-HIAA (5-HT metabolic product), but did not influence the concentrations of DynA(1-13), OXT, the other classical neurotransmitters and their metabolic products. PAG pretreatment with naloxone - an opiate receptor antagonist completely attenuated the pain threshold increase induced by PAG administration of AVP, but local pretreatment of OXT or classical neurotransmitter receptor antagonist did not influence the pain threshold increase induced by PAG administration of AVP. The data suggested that AVP in PAG could induce the local release of enkephalin and endorphin rather than dynophin, OXT and classical neurotransmitters to participate in pain modulation.

Arginine vasopressin in periaqueductal gray, which relates to antinociception, comes from hypothalamic paraventricular nucleus in the rat

Hypothalamic paraventricular nucleus (PVN) is a major source of arginine vasopressin (AVP). Our previous work has proven that: (1) pain stimulation enhances PVN synthesis and secretion of AVP; (2) AVP in periaqueductal gray (PAG) plays a role in antinociception; (3) pain stimulation increases AVP concentration in PAG tissue. The present study was to investigate AVP source in PAG during pain modulation of the rat. The results showed that: (1) pain stimulation elevated AVP concentration in both PVN and PAG perfusion liquid, in which the peak of AVP concentration in PVN perfusion liquid occurred earlier than that in PAG perfusion liquid; (2) PVN cauterization weakened pain stimulation-induced PAG releasing AVP, in which the inhibitive effect of bilateral PVN cauterization showed stronger than that of unilateral PVN cauterization; (3) microinjection of l-glutamate sodium into PVN, which excited local neurons, increased AVP concentration in PAG perfusion liquid in a dose-dependent manner. The data suggest that AVP in PAG, which relates with pain modulation, comes from PVN.

Through V2, not V1 receptor relating to endogenous opiate peptides, arginine vasopressin in periaqueductal gray regulates antinociception in the rat

Our previous study has proven that central arginine vasopressin (AVP) plays an important role in antinociception, and pain stimulation raises AVP concentration in the periaqueductal gray (PAG). The nociceptive effect of AVP in PAG was investigated in the rat. The results showed that microinjection of AVP into PAG increased pain threshold, whereas microinjection of V2 receptor antagonist-d(CH2)5[d-Ile2, Ile4, Ala9-NH2]AVP into PAG decreased pain threshold in a dose-dependent manner, but local administration of V1 receptor antagonist-d(CH2)5Tyr(Me)AVP did not change pain threshold; Pain stimulation elevated AVP, Leucine-enkephalin (L-Ek), Methionine-enkephalin (M-Ek) and beta-endorphin (beta-Ep), not dynorphinA(1-13) (DynA(1-13)) concentrations in PAG perfuse liquid; PAG pre-treatment with naloxone, an opiate receptor antagonist or V2 receptor antagonist completely reversed AVP-induced increase in pain threshold, however, PAG pre-treatment with V1 receptor antagonist did not influence this effect of AVP administration. The data suggest that AVP in the PAG, through V2 rather than V1 receptor, regulates antinociception, which progress relates to enkephalin and endorphin.

Effect of arginine vasopressin in the nucleus raphe magnus on antinociception in the rat

Previous work has shown that arginine vasopressin (AVP) regulates antinociception through brain nuclei rather than the spinal cord and peripheral organs. The present study investigated the nociceptive effect of AVP in the nucleus raphe magnus (NRM) of the rat. Microinjection of AVP into the NRM increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH2)5Tyr(Et)DAVP decreased the pain threshold. Pain stimulation elevated AVP concentration in the NRM perfuse liquid. NRM pretreatment with AVP-receptor antagonist completely reversed AVPs effect on pain threshold in the NRM. The data suggest that AVP in the NRM is involved in antinociception.

Arginine vasopressin is an important regulator in antinociceptive modulation of hypothalamic paraventricular nucleus in the rat.

Our previous study has proven that hypothalamic paraventricular nucleus (PVN) stimulation increases pain threshold and PVN cauterization decreases pain threshold. The studied neuropeptides in PVN were investigated to involve to pain modulation in the rat. The results showed that (1) intraventricular injection (icv) of anti-arginine vasopressin (AVP) serum completely reversed pain threshold increase induced by l-glutamate sodium (Glu) injection into the PVN, and local administration (icv) of anti-leucine-enkephalin (L-Ek) serum or anti-beta-endorphin (beta-Ep) serum partly attenuated pain threshold increase induced by Glu injection into the PVN, but pre-treatment of anti-oxytocin (OXT), dynorphinA(1-13) (DynA(1-13)), cholecystokinin-like peptide (CCK), neurotensin (NT), corticotrophin-releasing hormone (CRH), adrenocorticotrophin (ACTH), somatostatin (SST), prolactin-releasing hormone (PRH), angiotensinII (AngII), vasoactive intestinal polypeptide (VIP), melanotropin-releasing hormone (MRH), thyrotropin-releasing hormone (TRH), substance P (SP) or growth hormone-releasing hormone (GHRH) serum (icv) did not influence the analgesic effect of PVN administration with Glu; (2) PVN stimulation with Glu elevated the concentrations of AVP, OXT, CCK, NT, CRH, SST, PRH and DynA(1-13) in PVN perfusion liquid, and could not change the concentrations of L-Ek, beta-Ep, AngII, ACTH, VIP, MRH, TRH, SP and GHRH in PVN perfusion liquid; (3) Pain stimulation increased the concentrations of AVP, L-Ek, beta-Ep, DynA(1-13), CRH and ACTH in PVN perfusion liquid, and did not alter the concentrations of OXT, CCK, NT, SST, PRH, AngII, VIP, MRH, TRH, SP and GHRH in PVN perfusion liquid. The data suggested that AVP played a more important role than the other studied peptides (OXT, L-Ek, beta-Ep, DynA(1-13), CCK, NT, CRH, ACTH, SST, PRH, AngII, VIP, MRH, TRH, SP and GHRH) in PVN antinociceptive progress.

Investigating the role of hypothalamic paraventricular nucleus in nociception of the rat.

The role of hypothalamic paraventricular nucleus (PVN) in nociception was investigated in the rat. Electrical stimulation of the PVN increased pain threshold, and microinjection of L-glutamate sodium into the PVN also elevated pain threshold in a dose-dependent manner, whereas cauterization of the PVN decreased pain threshold. Stimulation or cauterization of the area located within 1.0 mm of the outer perimeter of the PVN did not change pain threshold. Pituitary removal could not influence the effect of L-glutamate sodium microinjection into PVN-induced pain threshold increase. The data suggest that PVN plays a role in antinociception through the central nervous system rather than peripheral organs.

RETRACTED: Periaqueductal gray knockdown of V2, not V1a and V1b receptor influences nociception in the rat

Our pervious study has proved that arginine vasopressin (AVP) in periaqueductal gray (PAG) plays a role in antinociception. After establishing a model of local special gene knockdown, the nociceptive effect of vasopressin receptor subunit in PAG was investigated in the rat. Microinjection of short-interfering RNA (siRNA) into PAG, which targeted vasopressin receptor subtypes (V(1a), V(1b) and V(2)), locally weakened the associated mRNA expression and depressed the related receptor synthesis in a dose-dependent manner, in which the significant inhibitive effect occurred on from 7th day to 14th day following 1microg or 2microg siRNA administration. PAG knockdown of V(2) receptor gene markedly decreased pain threshold in from 6th day to 13th day after siRNA administration, whereas local knockdown of either V(1a) or V(1b) receptor gene could not influence pain threshold. The data suggest that V(2) rather than V(1a) and V(1b) receptor in PAG involves in nociception.

Arginine vasopressin antinociception in the rat nucleus raphe magnus is involved in the endogenous opiate peptide and serotonin system.

Arginine vasopressin (AVP) in the nucleus raphe magnus (NRM) has been implicated in antinociception. This communication was designed to investigate which neuropeptide and neurotransmitter are involved in AVP antinociception in the rat NRM. The results showed that (1) in the NRM perfuse liquid, pain stimulation could increase the concentrations of AVP, leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), beta-endorphin (beta-Ep), serotonin (5-HT) and 5-hydroxyindoleacetic acid (5-HIAA), but not change the concentrations of dynorphinA(1-13) (DynA(1-13)), oxytocin, achetylcholine, choline, gamma-aminobutyric acid, glutamate, dopamine, 3,4-dihydroxyphenylacetic acid, homovanilic acid, norepinephrine and epinephrine; (2) in the NRM perfuse liquid, AVP increased the concentrations of L-Ek, M-Ek, beta-Ep, DynA(1-13), 5-HT and 5-HIAA, but did not change the concentrations of oxytocin and the other studied neurotransmitters; (3) AVP antinociception in the NRM was attenuated by cypoheptadine (a 5-HT-receptor antagonist) or naloxone (an opiate receptor antagonist), but was not influenced by the other studied receptor antagonists. The data suggested that AVP antinociception in the NRM might be involved in endogenous opiate peptide and 5-HT system.

Dynorphin A enhances mitogen-induced proliferative response and interleukin-2 production of rat splenocytes☆

It has been well known that immune function is modulated by endogenous opioid peptides: beta-endorphin and enkephalins. However, the effect of dynorphin A on the immune function has not been well documented. In this study, we investigated dynorphin A in the regulation of mitogen-induced proliferation and and interleukin-2 (IL-2) production of rat splenocytes. The results showed that dynorphin A 1-13 as well as dynorphin A 1-17 enhanced concanavalin A-stimulated [(3)H] thymidine uptake 46-112% and IL-2 production in a dose-dependent fashion. These effects were reversed by naloxone and norBNI, a selective kappa-receptor antagonist. Dynorphin A reduced cyclic AMP contents in spenocytes in naloxone and norBNI reversible fashion. The data suggest that dynorphin A enhanced mitogen-stumulated lymphocyte proliferation and IL-2 production via kappa-opioid receptor and cAMP pathway.