Spontaneous regression of a large sequestered lumbar disc herniation: a case report and literature review.

Lumbar disc herniation is a common disorder in adults that is accompanied by lower back and radicular pain. A 32-year-old man visited our clinic with 1-week history of persistent lower back pain and weakness in his right big toe. Magnetic resonance imaging (MRI) of his lumbar spine revealed herniated discs at L3/L4, L5/S1 and L4/L5, where a right-sided intraspinal mass lesion deep to the L4 vertebral body was causing compression of the nerve root. The patient underwent conservative treatment and reported no symptoms referrable to his back or leg 4 months later. Follow-up MRI showed no herniation of the nucleus pulposus at the L4/L5 level or lesion deep to the vertebral body of L4, whereas no changes had occurred to the status of the herniated L3/L4 and L5/S1 discs. The present case and a literature review show that a sequestered lumbar disc herniation can regress within a relatively short timeframe without surgery. The authors emphasise the utility of conservative therapy for patients who do not have a definitive surgical indication.

Novel inflammatory markers in the blood of patients with knee synovitis.

OBJECTIVE: Synovitis is a joint disease that seriously affects patient quality of life, but there are currently no diagnostic markers. The albumin to fibrinogen ratio (AFR) and monocyte to lymphocyte ratio (MLR) are non-invasive and cost-effective markers for various systemic inflammatory diseases. However, these markers have not yet been investigated for synovitis. This cross-sectional study evaluated the predictive ability of AFR and MLR in patients with non-specific knee synovitis. METHODS: One hundred fifty-five patients with knee synovitis and 108 healthy control patients were enrolled. Patient characteristics, blood parameters, AFRs, and MLRs were assessed, and the diagnostic value of these factors was determined. RESULTS: Among 125 patients included, patients with synovitis had a lower AFR and higher MLR than control subjects. The diagnostic values of AFR and MLR were 0.86 and 0.84, respectively, and higher compared with other parameters by receiver operating characteristic curve assessments. Additionally, MLR was negatively correlated with AFR. Late-stage patients showed significantly lower AFRs and significantly higher MLRs than early-stage patients. Binary logistic regression analyses indicated that AFR was an independent predictor for synovitis severity. CONCLUSIONS: The AFR and MLR had high diagnostic value for knee synovitis. The AFR was an independent predictor for synovitis severity.

Oxytocin in hypothalamic supraoptic nucleus is transferred to the caudate nucleus to influence pain modulation.

Oxytocin (OXT), which is synthesized and secreted in the hypothalamic supraoptic nucleus (SON), is the most important bioactive substance in SON regulating pain process. Our previous study has pointed that OXT in the caudate nucleus (CdN) plays a role in pain modulation. The communication was designed to investigate the source of OXT in the rat CdN during pain process using the methods of push-pull perfusion and radioimmunoassay. The results showed that (1) pain stimulation increased the OXT concentration in the CdN perfusion liquid; (2) SON cauterization inhibited the increase of OXT concentration in CdN perfusion liquid induced by the pain stimulation, which role in both sides of SON cauterization was stronger than that in one side of SON cauterization; and (3) SON microinjection of l-glutamate sodium, which excited the SON neurons, increased OXT concentration in the CdN perfusion liquid. The data suggested that OXT in the CdN was influenced by SON during pain process, i.e., OXT in the SON might be transferred to the CdN to influence pain modulation.

Effect of arginine vasopressin on the cortex edema in the ischemic stroke of Mongolian gerbils.

Brain edema formation is one of the most important mechanisms of ischemia-evoked cerebral edema. It has been demonstrated that arginine vasopressin (AVP) receptors are involved in the pathophysiology of secondary brain damage after focal cerebral ischemia. In a well-characterized animal model of ischemic stroke of Mongolian gerbils, the present study was undertaken to clear the effect of AVP on cortex edema in cerebral ischemia. The results showed that (1) occluding the left carotid artery of Mongolian gerbils not only decreased the cortex specific gravity (cortex edema) but also increased AVP levels in the ipsilateral cortex (ischemic area) including left prefrontal lobe, left parietal lobe, left temporal lobe, left occipital lobe and left hippocampus for the first 6 hours, and did not change of the cortex specific gravity and AVP concentration in the right cortex (non-ischemic area); (2) there were many negative relationships between the specific gravity and AVP levels in the ischemic cortex; (3) intranasal AVP (50 ng or 200 ng), which could pass through the blood-brain barrier to the brain, aggravated the focal cortex edema, whereas intranasal AVP receptor antagonist-D(CH2)5Tyr(ET)DAVP (2 µg) mitigated the cortex edema in the ischemic area after occluding the left carotid artery of Mongolian gerbils; and (4) either intranasal AVP or AVP receptor antagonist did not evoke that edema in the non-ischemic cortex. The data indicated that AVP participated in the process of ischemia-evoked cortex edema, and the cerebral AVP receptor might serve as an important therapeutic target for the ischemia-evoked cortex edema.

Norepinephrine plays an important role in antinociceptive modulation of hypothalamic paraventricular nucleus in the rat.

Our previous study has proven that hypothalamic paraventricular nucleus (PVN) plays a role in antinociception. The effects of studied classical neurotransmitter on PVN antinociceptive modulation were investigated in the rat. The results showed: (1) Pain stimulation increased norepinephrine (NE), but not epinephrine, dopamine (DA), 3,4-dihydroxyphenylacetic acid (DA metabolic product), homovanilic acid (DA metabolic product), serotonin (5-HT), 5-hydroxyindoleacetic acid (5-HT metabolic product), acetycholine (Ach), choline (Ach metabolic product), gamma-aminobutyric acid (GABA), and L-glutamate acid concentrations in the PVN perfusion liquid; (2) PVN stimulation with L-glutamate sodium, which excited local neurons only, did not influence the concentrations of the studied classical neurotransmitter and metabolic product in the PVN perfusion liquid; (3) Microinjection of NE, epinephrine, or L-glutamate sodium into the PVN elevated pain threshold, and local administration of GABA decreased pain threshold in a dose-dependent manner, but PVN administration of Ach, DA, or 5-HT did not change pain threshold; (4) Microinjection of phentolamine (alpha-receptor antagonist) or MK801 [NMDA-receptor antagonist] into the PVN reduced pain threshold, and local administration of bicuculline (GABA-receptor antagonist) raised pain threshold, but PVN administration of propranolol (beta-receptor antagonist), atropine (Muscarinic cholinergic receptor antagonist), 6-OH gallamine (Nicotinic cholinergic receptor antagonist), fluperidol (DA-receptor antagonist), or cyproheptadine (5-HT-receptor antagonist) did not alter pain threshold. The data suggested that endogenous NE, not epinephrine, 5-HT, Ach, GABA, and L-glutamate acid played an important role in the PVN antinociceptive modulation.

Arginine vasopressin induces rat caudate nucleus releasing acetylcholine to participate in pain modulation.

A lot of studies have pointed that acetylcholine (Ach), a classic neurotransmitter can regulate pain process in the caudate nucleus (CdN). Our previous report has proven that arginine vasopressin (AVP) effects on pain modulation in the CdN. The communication was designed to investigate the interaction between AVP and Ach in the rat CdN during the pain process. AVP concentration was determined by radioimmunoassay (RIA) and Ach concentration by high performance liquid chromatography (HPLC). The results showed that pain stimulation increased both AVP and Ach concentrations in the CdN perfusion liquid; AVP increased Ach concentration in the CdN perfusion liquid, while AVP receptor antagonist including d(CH(2))(5)Tyr(Me)AVP (V(1) receptor antagonist) and d(CH(2))(5)[D-Ile(2), Ile(4), Ala-NH(2)(9)]AVP (V(2) receptor antagonist) decreased Ach concentration in the CdN perfusion liquid. The data indicated that the analgesic effect of AVP might be involved in the Ach system in the CdN.

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.

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.

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.

Effect of arginine vasopressin on acupuncture analgesia in the rat.

Arginine vasopressin (AVP) has been proven to be involved in the process of pain regulation. This communication was designed to investigate the effect of AVP on acupuncture analgesia in the rat model. The results showed that intraventricular injection (icv) of AVP could enhance acupuncture analgesia in a dose-dependent manner, whereas icv of anti-AVP serum decreased acupuncture analgesia. However, neither intrathecal (ith) nor intravenous injection (iv) of AVP or anti-AVP serum could influence acupuncture analgesia. Electrical acupuncture of "Zusanli" points (St. 36) decreased AVP concentration in the hypothalamic paraventricular nucleus (PVN), and increased AVP concentration in the hypothalamic supraoptic nucleus (SON), periaqueductial gray (PAG), caudate nucleus (CdN) and raphe magnus nucleus (RMN), but did not change AVP concentration in the pituitary, spinal cord and plasma. The effect of AVP on acupuncture analgesia was partly reversed by pretreatment with naloxone, an opiate receptor antagonist. These data suggested that AVP in the brain played a role in the process of acupuncture analgesia in combination with the endogenous opiate peptide system.

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.

Effect of oxytocin on acupuncture analgesia in the rat.

Oxytocin has been demonstrated to be involved in pain modulation. Acupuncture analgesia is a very useful clinical tool for pain relief, which has over 2500-year history in China. The present study investigated the role of oxytocin in acupuncture analgesia in the rat through oxytocin administration and measurement. Central administration of oxytocin (intraventricular injection or intrathecal injection) enhanced acupuncture analgesia, while central administration of anti-oxytocin serum weakened acupuncture analgesia in a dose-dependent manner. However, intravenous injection of oxytocin or anti-oxytocin serum did not influence acupuncture analgesia. Electrical acupuncture of "Zusanli" (St. 36) reduced oxytocin concentration in the hypothalamic supraoptic nucleus, and elevated oxytocin concentration in the hypothalamic suprachiasmatic nucleus, hypothalamic ventromedial nucleus, thalamic ventral nucleus, periaqueductal gray, raphe magnus nucleus, caudate nucleus, thoracic spinal cord and lumbar spinal cord, but did not alter oxytocin concentration in the hypothalamic paraventricular nucleus, anterior pituitary, posterior pituitary and plasma. The data suggested that oxytocin in central nervous system rather than in peripheral organs is involved in acupuncture analgesia.

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 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.

Periaqueductal gray knockdown of V2, not V1a and V1b receptor influences nociception in the rat. yj6676@yahoo.com.

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 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.

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.

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.

Arginine vasopressin in the caudate nucleus plays an antinociceptive role in the rat.

Our 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 caudate nucleus (CdN) of the rat. Microinjection of AVP into the CdN increased pain threshold in a dose-dependent manner, while local administration of AVP-receptor antagonist-d(CH(2))(5)Tyr(Et)DAVP decreased pain threshold. Pain stimulation elevated AVP concentration in CdN perfuse liquid. CdN pretreatment with AVP-receptor antagonist completely reversed AVP's effect on pain threshold in the CdN. The data suggest that AVP in the CdN is involved in antinociception.