Hong-Tao Xu

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.

Arginine vasopressin enhances periaqueductal gray synthesis and secretion of enkephalin and endorphin in the rat

Previous study has proven that arginine vasopressin (AVP) enhances periaqueductal gray (PAG) secreting enkephalin and endorphin in vivo in the rat. Present work investigated that AVP effect on PAG secretion and synthesis of enkephalin and endorphin in vitro. Radioimmunoassy results showed that AVP increased leucine-enkephalin (L-Ek), methionine-enkephalin (M-Ek), beta-endorphin (beta-Ep) rather than dynorphin A(1-13) (DynA(1-13)) concentrations in PAG slice culture liquid, and V(2) receptor antagonist: d(CH(2))(5)[D-Ile(2), Ile(4), Ala(9)-NH(2)]AVP decreased L-Ek, M-Ek and beta-Ep, not DynA(1-13) concentrations in PAG slice culture liquid in a dose-dependent manner, but V(1) receptor antagonist: d(CH(2))(5)Tyr(Me)AVP did not change these peptide concentrations in PAG slice culture liquid. RT-PCR data displayed that AVP enhanced proenkephalin and proopiomelanocortin (Pro-beta-Ep) rather than prodynorphin mRNA expressions in culture PAG tissues, and V(2) receptor antagonist weakened proenkephalin and proopiomelanocortin (Pro-beta-Ep), not prodynorphin mRNA expressions in culture PAG tissues, but V(1) receptor antagonist did not influence these mRNA expressions in culture PAG tissues. The data suggest that AVP enhances PAG synthesizing and secreting enkephalin and endorphin rather than dynorphin through V(2) receptors.

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.

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.

Endogenous opiate peptides in the spinal cord are involved in the analgesia of hypothalamic paraventricular nucleus in the rat

Many studies have shown that hypothalamic paraventricular nucleus (PVN) plays a role in pain process, and endogenous opiate peptide system in the spinal cord is involved in nociception. This communication was designed to study the relationship between PVN and endogenous opiate system in the spinal cord in the rat. The results showed that in both the thoracic and the lumber spinal cord, microinjection of 100 ng L-glutamate sodium into PVN could increase leucine-enkephalin (L-Ek), beta-endorphin (beta-Ep), dynorphinA(1-13) (DynA(1-13)) concentrations and PVN cauterization decreased L-Ek and beta-Ep concentrations. Pretreatment of the spinal cord with 5 microg naloxone, an opiate receptor antagonist could partly reverse the analgesia induced by microinjection of 100 ng L-glutamate sodium into PVN. The data suggested that PVN analgesia might be involved in the endogenous opiate peptide system in the spinal cord independently.

Arginine vasopressin in hypothalamic paraventricular nucleus is transferred to the nucleus raphe magnus to participate in pain modulation

Hypothalamic paraventricular nucleus (PVN) is one of the main sources of arginine vasopressin (AVP) synthesis and secretion. AVP is the most important bioactive substance in PVN regulating pain process. Our previous study has pointed that pain stimulation induced AVP increase in the nucleus raphe magnus (NRM), which plays a role in pain modulation. The present study was designed to investigate the source of AVP in the rat NRM during pain process using the methods of nucleus push-pull perfusion and radioimmunoassay. The results showed that pain stimulation increased the AVP concentration in the NRM perfusion liquid, PVN cauterization inhibited the role that pain stimulation induced the increase of AVP concentration in the NRM perfusion liquid, and PVN microinjection of L-glutamate sodium, which excited the PVN neurons, could increase the AVP concentration in the NRM perfusion liquid. The data suggested that AVP in the PVN might be transferred to the NRM to participate in pain modulation.

Norepinephrine regulates arginine vasopressin secretion in hypothalamic paraventricular nucleus relating with pain modulation

Our previous study has pointed that arginine vasopressin (AVP) and norepinephrine (NA) are two most important bioactive substances that play a role in hypothalamic paraventricular nucleus (PVN) regulating pain process. The communication was designed to investigate the interaction between AVP and NA in the rat PVN during the pain process. We used the potassium iontophoresis inducing tail-flick to test the pain threshold, PVN push-pull perfusion to collect the samples, high performance chromatography (HPLC) to determine the NA concentration and radioimmunoassay (RIA) to measure the AVP concentration. The results showed that (1) pain stimulation increased both NA and AVP concentrations in the PVN perfusion liquid; (2) PVN administration of l-glutamate sodium increased AVP, not NA concentration in the PVN perfusion liquid; (3) AVP or d(CH(2))(5)Tyr(Et)DAVP (AVP-receptor antagonist) neither changed pain threshold, nor influenced NA concentration in the PVN perfusion liquid; (4) Microinjection of NA into PVN could increase pain threshold in a dose-dependent manner, while PVN administration with phentolamine (alpha-receptor antagonist), not propranolol (beta-receptor antagonist) decreased pain threshold; (5) Administration of NA increased AVP concentration, while phentolamine, not propranolol decreased AVP concentration in the PVN perfusion liquid. These data suggested that it is through alpha-receptor rather than beta-receptor, NA induced PVN secretion of AVP that was delivered to the related brain regions to participate in pain modulation.