Increasing sympathetic nerve terminal-dependent plasma extravasation correlates with decreased arthritic joint injury in rats

doi:10.1016/0306-4522(91)90184-P

Neuroscience

Volume 40, Issue 1, 1991, Pages 185-189

https://doi.org/10.1016/0306-4522(91)90184-P Get rights and content

Abstract

This study compared the pharmacology of adrenergic agents that influence plasma extravasation in normal animals with those agents that influence tissue injury in an inflammatory disease model. Specifically we studied the effects of beta₂- and alpha₂-adrenergic receptor agonists and antagonists on bradykinin-induced plasma extravasation in normal Sprague-Dawley rats and on joint injury in rats with experimental arthritis. Plasma extravasation induced by infusion of bradykinin in the rat knee joint was attenuated by the beta₂-agonist salbutamol or by the alpha₂-antagonist yohimbine, and was enhanced by the beta₂-antagonist, ICI-118,551, or by the alpha₂agonist, clonidine. In rats that had undergone chemical sympathectomy, bradykinin-induced plasma extravasation was markedly reduced, and there was no enhancement of bradykinin-induced plasma extravasation by either ICI-118,551 or clonidine.

Although ICI-118,551 and clonidine enhanced bradykinin-induced plasma extravasation, these drugs significantly reduced joint injury in rats with adjuvant-induced arthritis. Neither salbutamol nor yohimbine, however, significantly increased joint injury in the arthritic rats, presumably because arthritis severity is already high in these animals. Consistent with this hypothesis, both salbutamol and yohimbine did significantly increase the joint injury associated with experimental arthritis in Wistar-Kyoto rats, a strain which develops a mild adjuvant arthritis.

The fact that increased plasma extravasation is associated with decreased arthritis severity suggests that plasma extravasation, a major sign of acute inflammation, contributes to tissue reparative processes.

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Cited by (53)

Dioclea violacea lectin ameliorates inflammation in the temporomandibular joint of rats by suppressing intercellular adhesion molecule-1 expression
2019, Biochimie
Citation Excerpt :
Therefore, the development of new drugs to treat inflammatory diseases from orofacial tissues continues to be of considerable importance to scientists. After tissue and/or neural damage the inflammatory response induces the local release of inflammatory chemical mediators, which in turn promote the inflammatory chemotaxis characterized by plasma extravasation and neutrophil migration [8]. Neutrophil is the main leukocyte involved in the host defense, whose intense influx into the injured tissue has been associated with the development and chronicity of inflammatory diseases, such as TMD [9].
Inflammation of temporomandibular joint (TMJ) tissues are the most common cause of pain conditions associated with temporomandibular disorders (TMDs). After a tissue and/or neural damage, the inflammatory response is characterized by plasma extravasation and leukocytes infiltration in the TMJ tissues, which in turn, release inflammatory cytokines cascades responsible for inflammatory pain. Lectins are glycoproteins widely distributed in nature that may exhibit anti-inflammatory properties. This study demonstrated by molecular docking and MM/PBSA that the lectin from Dioclea violacea (DVL) interacts favorably with α-methyl-D-mannoside, N-acetyl-D-glucosamine, and core1-sialyl-Lewis X which are associated with leukocytes migration during an inflammatory response. Wistar rats pretreated with intravenously injection of DVL demonstrated a significant inhibition of plasma extravasation induced by carrageenan (a non-neurogenic inflammatory inductor) and mustard oil (a neurogenic inflammatory inductor) in the TMJ periarticular tissues (p < 0.05; ANOVA, Tukey's test). In addition, DVL significantly reduced carrageenan-induced leukocyte migration in the TMJ periarticular tissues mediated by down-regulation of ICAM-1 expression. These results suggest a potential anti-inflammatory effect of DVL in inflammatory conditions of TMJ.
Neurogenic Regulation of Bradykinin-Induced Synovitis
2009, NeuroImmune Biology
Citation Excerpt :
The role of the sympathetic postganglionic neuron in inflammation has been most extensively studied in the synovium (see Ref. [16] for review). For example, selective activation of the sympathetic postganglionic neuron terminal with 6-hydroxydopamine, to displace sympathetic neurotransmitters from vesicular stores [70,71], increases plasma extravasation in the rat knee joint [72], and plasma extravasation is decreased by surgical [73–79] or chemical (with guanethidine or 6-hydroxydopamine) [72,80–89] sympathectomy. In particular, surgical or chemical sympathectomy attenuates the magnitude of both basal plasma extravasation and that induced by bradykinin, a principal inflammatory mediator, in the rat knee joint by 60–70% [88,90,91] and producing a large leftward shift in the dose–response curve for bradykinin (Fig. 2).
Substantial evidence is described supporting the hypothesis that bradykinin-induced synovial inflammation is dependent on the sympathetic postganglionic neuron. In addition, experimental data indicate that a sympathetic–C-fiber afferent neuron integration plays a role in acute and chronic inflammation in the synovium and other tissues. For example, sympathetic–C-fiber coupling takes place during the skin inflammatory response [146,212,213]. Specifically, sympathetic efferent activity acts on peripheral adrenergic receptors to enhance C-fiber sensitization, thereby augmenting the generation of dorsal root reflexes that produce vasodilatation. However, to firmly establish such integration in synovial tissue, further studies are needed that employ controlled selective activation of the afferents supplying the synovium, e.g., by electrical stimulation of the corresponding dorsal roots [211].
Furthermore, the evidence suggests that there exists a functionally distinct sympathetic efferent pathway that enables the central nervous system to modulate the inflammatory response by acting on components of the immune system [103,116]. Specifically, at a systemic level activity in the sympathetic neurons modulates immune cell function via innervation of lymphoid organs and by direct contact with lymphocytes and macrophages [214], and at the local level the sympathetic modulates the sensitivity of nociceptors, directly or via immune cells and their signaling molecules (e.g., cytokines). A schematic representation of the interaction of some key systems in the control of synovial inflammation is shown in Fig. 4.
Peripheral Sympathetic Component of the Temporomandibular Joint Inflammatory Pain in Rats
2006, Journal of Pain
Citation Excerpt :
In addition to prostaglandins, sympathomimetic amines such as norepinephrine are also released at the site of inflammation,20,33 where they contribute to the inflammatory hyperalgesia.2,27 Therefore, our finding that depletion of intracellular stores of norepinephrine by guanethidine significantly attenuated the TMJ hyperalgesia induced by carrageenan indicates that norepinephrine contributes to the hyperalgesic state in the TMJ, as previously demonstrated in other tissues.14,15,16,33,46 This finding is consistent with the dense innervation of the temporomandibular joint by sympathetic fibers arising from cells of the superior cervical ganglion28,50,51 from where norepinephrine may be released.
The aim of this study was to further validate our carrageenan-induced temporomandibular joint (TMJ) inflammatory hyperalgesia model in rats by showing that administration of indomethacin before the initiation of inflammation would diminish the TMJ hyperalgesia. Using this model, we investigated whether norepinephrine and local β-adrenoceptors contribute to the development of inflammatory TMJ hyperalgesia. Carrageenan-induced TMJ hyperalgesia was assessed by measuring the behavioral nociceptive responses, such as rubbing the orofacial region and flinching the head, induced by the injection of a low dose of 5-hydroxytryptamine into the TMJ sensitized 1 h before by a TMJ injection of carrageenan. Blockade of prostaglandin synthesis by indomethacin prior to initiation of inflammation by carrageenan significantly attenuated the TMJ hyperalgesia. The guanethidine depletion of norepinephrine or the blockade of β₂ but not the blockade of the β₁-adrenoceptor by the selective adrenoceptor antagonists ICI 118.55 and atenolol, respectively, significantly reduced carrageenan-induced TMJ hyperalgesia. In the present study, we further validated our carrageenan-induced TMJ hyperalgesia model to study the mechanisms involved in inflammatory TMJ hyperalgesia and to test the analgesic effect of different types of peripheral analgesics. We also demonstrated that norepinephrine released at the site of injury contributes to the development of the inflammatory TMJ hyperalgesia by the activation of β₂-adrenoceptors.
The findings that local sympathomimetic amines contribute to the inflammatory TMJ hyperalgesia by activating β₂-adrenoceptors may be relevant to clinical TMJ inflammatory pain states less sensitive to nonsteroidal anti-inflammatory drugs.
Intrathecal neostigmine reduces the zymosan-induced inflammatory response in a mouse air pouch model via adrenomedullary activity: Involvement of spinal muscarinic type 2 receptors
2005, Neuropharmacology
Intrathecal (IT) injection of neostigmine (a cholinesterase inhibitor) has been reported to produce a significant anti-nociceptive effect in a number of inflammatory pain models. However, a potential anti-inflammatory effect of IT neostigmine in these models has not been investigated. In the present study, we have examined the ‘anti-inflammatory effect of IT injection of neostigmine’ (AI-NEO) using a standard mouse air pouch model by evaluating the effect of AI-NEO on zymosan-induced leukocyte migration and myeloperoxidase (MPO) release. IT neostigmine was found to suppress both leukocyte migration and MPO degranulation in a dose dependent manner. We then established which subtypes of cholinergic receptors were involved in this AI-NEO. IT pretreatment with atropine (a muscarinic receptor antagonist) but not hexamethonium (a nicotinic receptor antagonist) completely blocked the IT neostigmine anti-inflammatory effect. Subsequent experiments showed that IT pretreatment with methoctramine (a muscarinic type 2 (M₂) receptor antagonist), but not pirenzepine (M₁ receptor antagonist) or 4-DAMP (M₃ receptor antagonist), suppressed the AI-NEO. We then evaluated whether adrenal glandular activity was important in the AI-NEO. Adrenalectomy significantly blocked the AI-NEO, while intraperitoneal pretreatment with the β-adrenoceptor antagonist (propranolol), but not the corticosteroid antagonist (RU486) reversed AI-NEO. In conclusion, these results indicate that IT neostigmine facilitates the activation of spinal M₂ receptors and this activation ultimately leads to release of adrenal catecholamines which contribute to the anti-inflammatory effect observed at the site of tissue inflammation.
Sympathetic neurotransmitters in joint inflammation
2005, Rheumatic Disease Clinics of North America
The importance of timing of adrenergic drug delivery in relation to the induction and onset of adjuvant-induced arthritis
2004, Brain, Behavior, and Immunity
Stressful events often precede onset and exacerbate established rheumatic diseases. There are numerous reports of abnormal autonomic function in rheumatoid arthritis (RA) patients. Targeting the sympathetic nervous system (SNS) with adrenergic receptor (AR) drugs in RA patients and animal models of the disease have revealed mixed results, with treatments inhibiting and exacerbating disease pathology. We tested the hypothesis that variability in disease outcome following adrenergic drug treatment is due to different roles played by the SNS at different disease stages. The contribution of β₂- and α-AR subtypes to disease pathology was studied at different disease stages in adjuvant-induced arthritis (AA), an animal model of RA. Lewis rats were given twice-daily intraperitoneal (i.p.) injections of an α-AR antagonist (phentolamine: 500 μg/kg) or a β₂-AR agonist (terbutaline: 1200 μg/day), initiated at adjuvant challenge or disease onset, and continued through severe disease. Both adrenergic therapies, when initiated at adjuvant challenge exacerbated disease pathology. In contrast, SH1293, an adrenergic drug that targets both α- and β-AR (300 μg/day; twice-daily), initiated at adjuvant challenge did not exacerbate disease severity. Additionally, the same treatment regimen of phentolamine, terbutaline or SH1293 initiated at disease onset attenuated joint-inflammation and dramatically reduced bone destruction in the arthritic hind limbs. These data support the SNS playing different roles in disease pathology preclinically and after disease onset. Given current drug therapies are not effective in preventing bone destruction, these data support using adrenergic drugs as bone sparing treatments in RA.

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^*: Present address: Pain Mechanisms Laboratory, Neuroscience Group, Clinical Research Institute of Montreal, Montreal, Québec, Canada H2W 1R7.

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Neuroscience

Abstract

References (25)

Anti-anaphylactic action in the mouse thyrotropin-releasing hormone (TRH) is mediated through beta₁-adrenoceptive effectors

Neurosci. Lett.

Discriminative stimulus properties of the vasodilator hydralazine: differential generalization with alpha₁ and alpha₂ adrenoceptor drugs

Prog. Neuropsychopharmac. biol. Psychiat.

Epinephrine exacerbates arthritis by an action at presynaptic beta₂-adrenoceptors

Neuroscience

Simultaneous measurements of macromolecular leakage and arteriolar blood flow as altered by PGE₁ and beta₂-stimulation in the hamster cheek pouch

Microvasc. Res.

Enhancement of the electrically induced release of norepinephrine from the rat portal vein: mediation by beta₂-adrenoceptors

Eur. J. Pharmac.

Effects of naproxen on connective tissue changes in the adjuvant arthritic rat

Arth. Rheum.

Studies on the acute inflammatory response. II. Influence of anti-histaminics and catecholamines on formaldehyde-induced edema

J. Pharmac. exp. Ther.

Neurol control of vascular permeability: interactions between primary afferents, mast cells and sympathetic efferents

J. Neurophysiol.

Blockade of histamine and bradykinin-induced increases in lymph flow, protein concentration, and protein transport by terbutaline in vivo

Microcirc. Res.

The chronic effects of beta-adrenoceptor antagonists on the efflux of tritiated noradrenaline from sympathetic nerves of the pithed rat

J. auton. Pharmac.

Possible role of an endogenous opiate in the cardiovascular effects of central alpha adrenoceptor stimulation in spontaneously hypertensive rats

J. Pharmac. exp. Ther.

The anti-inflammatory effect of catecholamines in the peritoneal cavity and hind paw of the mouse

Br. J. Pharmac.

Cited by (53)

Dioclea violacea lectin ameliorates inflammation in the temporomandibular joint of rats by suppressing intercellular adhesion molecule-1 expression

Neurogenic Regulation of Bradykinin-Induced Synovitis

Peripheral Sympathetic Component of the Temporomandibular Joint Inflammatory Pain in Rats

Intrathecal neostigmine reduces the zymosan-induced inflammatory response in a mouse air pouch model via adrenomedullary activity: Involvement of spinal muscarinic type 2 receptors

Sympathetic neurotransmitters in joint inflammation

The importance of timing of adrenergic drug delivery in relation to the induction and onset of adjuvant-induced arthritis