Neurogenic influences on contralateral responses during experimental rat monoarthritis

Kidd, Bruce L.; Cruwys, Simon; Garrett, Neil; Mapp, P.I.; Jolliffe, Victoria; Blake, David R.

doi:10.1016/0006-8993(95)00512-o

Cited by 43 publications

(27 citation statements)

References 17 publications

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“…Regarding arthritic joints, it is thought that a neurogenic component is responsible for the symmetrical joint involvements, and that this is related to primary-afferent activation on one side, secondarily leading to contralateral activation of homologous afferents 19. The fact that the contralateral responses seen upon experiments for limbs are topographically precise20 indeed suggests that the contralateral responses seen in these experiments imply a neurogenic mechanism rather than systemic effects. It has actually became clear that the contralateral responses are stimulus specific, that is, if the unilateral stimulus is pro-inflammatory, the contralateral response is also proinflammatory 21.…”

Section: Discussionmentioning

confidence: 92%

Unilateral surgical treatment for patients with midportion Achilles tendinopathy may result in bilateral recovery

2012

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Section: Discussionmentioning

confidence: 92%

Unilateral surgical treatment for patients with midportion Achilles tendinopathy may result in bilateral recovery

2012

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“…There is a growing body of evidence that unilateral nerve injury evokes bilateral responses (Kidd et al 1995;Chudler et al 1997;Yamaguchi et al 1999), but the underlying mechanisms are largely unknown. Possible mechanisms of contralateral signaling were reviewed by Koltzenburg et al (1999).…”

Section: Discussionmentioning

confidence: 99%

Bilateral Changes in IL-6 Protein, but not in its Receptor gp130, in Rat Dorsal Root Ganglia Following Sciatic Nerve Ligature

et al. 2009

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Local intracellular signaling cascades following peripheral nerve injury lead to robust axon regeneration and neuropathic pain induction. Cytokines are classic injury-induced mediators. We used sciatic nerve ligature (ScNL) to investigate temporal changes in IL-6 and its receptor gp130 in both ipsilateral and contralateral lumbal (L4-L5) dorsal root ganglia (DRG). Rats were operated aseptically on unilateral ScNL and allowed to survive for 1, 3, 7, and 14 days. Immunohistochemistry and Western blot analysis were used to determine levels of IL-6 and gp130 in DRG. A distinct increase in immunostaining for IL-6 was found in the neuronal cell bodies of sections through both ipsilateral and contralateral DRG at 1 and 3 days after operation. After 7 and 14 days, the DRG sections displayed only a moderate elevation in immunostaining when compared with sections of naïve DRG. The levels of IL-6 protein increased in both ipsilateral and contralateral lumbal DRG following peripheral nerve injury. The elevation of IL-6 protein was significant in both ipsilateral and contralateral DRG 1, 3, 7, and 14 days after operation. On the other hand, the levels of gp130 receptor did not change significantly. The data provide evidence for changes in IL-6 levels not only in the DRG associated with the damaged nerve but also in those unassociated with nerve injury during the experimental neuropathic pain model.

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“…In addition, there exists considerable evidence for a role of the nervous system in the hallmark bilateral symmetry of RA [39]. In fact, several animal studies have shown that induction of monoarthritis in one joint can lead to pathology in the contralateral untreated joint [40,41]. However, despite possible roles for other pathways in conferring the observed contralateral effect, our data strongly suggest that local intra-articular gene expression has a major function in conferring a contralateral effect in part through modulation of function of resident APCs.…”

Section: Discussionmentioning

confidence: 99%

Ex Vivo Gene Delivery of IL-1Ra and Soluble TNF Receptor Confers a Distal Synergistic Therapeutic Effect in Antigen-Induced Arthritis

et al. 2002

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Intra-articular expression of antagonists of interleukin-1beta (IL-1beta) and tumor necrosis factor-alpha (TNF-alpha) in arthritic rabbit knee and mouse ankle joints by direct adenoviral-mediated intraarticular delivery results in amelioration of disease pathology in both the treated and contralateral untreated joints. Previous experiments suggest that direct adenoviral infection of resident antigen-presenting cells (APCs) and subsequent traveling of these cells to other sites of inflammation and lymph nodes might be responsible for this "contralateral effect." To determine whether genetic modification of APCs is required for the contralateral effect, we have used an ex vivo approach utilizing genetically modified fibroblasts to express IL-1 receptor antagonist protein (IL-1Ra) and soluble TNF-alpha receptor (sTNFR) locally in arthritic joints. Retroviral vectors carrying IL-1Ra, sTNFR-Ig, or both genes together were used to stably infect autologous rabbit fibroblasts that were then injected intra-articularly into arthritic rabbit knee joints. The intra-articular delivery of either IL-1Ra- or sTNFR-Ig-expressing fibroblasts was antiinflammatory and chondro-protective in both the injected and noninjected contralateral joints. In addition, we demonstrate that the co-delivery of both antagonists in combination results in a synergistic effect in disease amelioration in both the treated and nontreated joints. These ex vivo results suggest that trafficking of vector-modified inflammatory cells is not the main mechanism responsible for the observed distal spread of the therapeutic effect. Moreover, the results demonstrate that local, ex vivo gene therapy for arthritis could be effective in blocking pathologies within untreated, distant arthritic joints.

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Neurogenic influences on contralateral responses during experimental rat monoarthritis

Cited by 43 publications

References 17 publications

Unilateral surgical treatment for patients with midportion Achilles tendinopathy may result in bilateral recovery

Unilateral surgical treatment for patients with midportion Achilles tendinopathy may result in bilateral recovery

Bilateral Changes in IL-6 Protein, but not in its Receptor gp130, in Rat Dorsal Root Ganglia Following Sciatic Nerve Ligature

Ex Vivo Gene Delivery of IL-1Ra and Soluble TNF Receptor Confers a Distal Synergistic Therapeutic Effect in Antigen-Induced Arthritis

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