Inhibition of inflammation and hyperalgesia in NK-1 receptor knock-out mice

Kidd, Bruce L.; Inglis, Julia J.; Vetsika, Kelly; Hood, Vivienne C.; Felipe, Carmen De; Bester, Hervé; Hunt, Stephen P.; Cruwys, Simon

doi:10.1097/00001756-200312020-00011

Cited by 24 publications

(17 citation statements)

References 13 publications

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“…Substance P stimulates acute plasma protein extravasation when injected into joints (39,40), although its possible role in more severe and chronic phases of disease is unclear (40,41). However, we have recently shown that there was no difference in responses in the CFA-induced model of joint inflammation, used in the present study, in WT versus neurokinin 1-knockout mice after 18 hours (20).…”

Section: Discussionmentioning

confidence: 59%

Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

Keeble¹,

Russell²,

Curtis³

et al. 2005

Arthritis & Rheumatism

154

117

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Objective. To investigate the endogenous involvement of transient receptor potential vanilloid 1 (TRPV1) in a model of knee joint inflammation in the mouse.Methods. Following characterization of wild-type (WT) and TRPV1-knockout mice, inflammation was induced via intraarticular (IA) injection of Freund's complete adjuvant (CFA). Knee swelling was assessed as diameter, and inflammatory heat hyperalgesia was determined using the Hargreaves technique, for up to 3 weeks. At 18 hours, acute hyperpermeability was measured with 125 I-albumin, and cytokines and myeloperoxidase activity, a marker of neutrophils, were assayed in synovial fluid extracts. The possibility that exogenous tumor necrosis factor ␣ (TNF␣) was involved in influencing TRPV1 activation was investigated in separate experiments.Results. Increased levels of knee swelling, hyperpermeability, leukocyte accumulation, and TNF␣ were found in WT mice 18 hours after IA CFA treatment compared with saline treatment. Significantly less knee swelling and hyperpermeability were found in TRPV1 ؊/؊ mice, but leukocyte accumulation and TNF␣ levels were similar in WT and TRPV1 ؊/؊ mice. Knee swelling in response to CFA remained significantly higher for a longer period in WT mice compared with TRPV1 ؊/؊ mice, with thermal hyperalgesic sensitivity observed at 24 hours and at 1 week in WT, but not TRPV1 ؊/؊ , mice. Knee swelling was attenuated (P < 0.05) in TRPV1 ؊/؊ compared with WT mice 4 hours after IA administration of TNF␣.Conclusion. Our findings indicate that TRPV1 has a role in acute and chronic inflammation in the mouse knee joint. Thus, selective antagonism of TRPV1 should be considered as a potential target for treatment of acute and chronic joint inflammation.

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Section: Discussionmentioning

confidence: 59%

Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

Keeble¹,

Russell²,

Curtis³

et al. 2005

Arthritis & Rheumatism

154

117

View full text Add to dashboard Cite

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“…As such, SP has been found to be associated with a number of inflammatory diseases (20,26,39,46). In support of these findings, SP induces production of proinflammatory cytokines TNF-␣, IL-1, IL-6, and IL-12 by macrophages (22,25).…”

Section: Discussionmentioning

confidence: 73%

Enhanced Immunoglobulin A Response and Protection againstSalmonella entericaSerovar Typhimurium in the Absence of the Substance P Receptor

et al. 2005

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The development of the neurokinin-1 receptor-deficient (NK1R−/−) mouse permitted inquiry into the regulation of secretory immunoglobulin A (S-IgA) responses by substance P (SP) after oral immunization with a Salmonella enterica serovar Typhimurium vector expressing colonization factor antigen I (CFA/I) from enterotoxigenic Escherichia coli. In NK1R−/− mice, mucosal and serum IgA anti-CFA/I fimbrial responses were augmented, while secreted IgG anti-CFA/I fimbrial responses remained unaffected compared to those of BALB/c (NK1R+/+) mice. Supportive antibody-forming cells were present in the small intestinal lamina propria and spleen. To gain insight as to why the augmented S-IgA responses occurred, minimally, the responses were not attributed to differences in vaccine colonization of Peyer's patch (PP) and spleen or in their respective tissue weights. However, these S-IgA responses were supported by increased numbers of PP CD4+ T helper (Th) cells secreting interleukin-5 (IL-5) and IL-6 and splenic CD4+ Th cells secreting IL-6 compared to NK1R+/+ mice. Challenge of naive NK1R−/− mice with wild-type Salmonella showed improved median survival compared to naive NK1R+/+ mice. Data from peritoneal macrophage infection studies suggest that this survival is in part contributed by increased IL-10 production. Oral vaccination with Salmonella CFA/I or Salmonella vector showed no significant differences in conferred protection against wild-type challenge for either NK1R−/− or NK1R+/+ mice. Thus, these studies suggest that SP mediation contributes to proinflammatory responses to Salmonella infections

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“…Moreover, intrathecal administration of the NK-1 antagonist L-732,138 reverses inflammation-induced hyperalgesia (Birch et al, 1992;Gao et al, 2003;Ren et al, 1996;Traub, 1996). NK-1 receptor knockout mice showed decreased sensitivity to inflammation-induced pain, showing decreased nociceptive behaviors during the second phase of the formalin response and reduced FOS-positive neurons within the spinal cord following formalin injection into the hindpaw (De Felipe et al, 1998) as well as reduced mechanical hypersensitivity following intraplantar Mycobacterium tuberculosus (Kidd et al, 2003). These data suggest that the neuroadaptive changes observed following prolonged exposure to sustained morphine are similar to those observed in inflammatory pain states, and that SP and the NK-1 receptor play a critical role in the mediation of hyperalgesia in both cases.…”

Section: Discussionmentioning

confidence: 99%

Role of NK-1 neurotransmission in opioid-induced hyperalgesia

King

Gardell

Wang

et al. 2005

Pain

Self Cite

153

128

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Opiates are among the most important drugs for treatment of moderate to severe pain and prolonged opiate administration is often required to treat chronic pain states. We investigated the neurobiological actions of sustained opiate administration revealing paradoxical pronociceptive adaptations associated with NK-1 receptor function. Sustained morphine delivered over 6 days elicited hyperalgesia in rats and mice during the period of opiate delivery. Sustained morphine administration increased substance P (SP) and NK-1 receptor expression in the spinal dorsal horn. Sustained morphine treatment also enhanced capsaicin-evoked SP release in vitro, and increased internalization of NK-1 receptors in response to noxious stimulation. While NK-1 receptor internalization was observed primarily in the superficial laminae of placebo-treated rats, NK-1 receptor internalization was seen in both superficial and deep lamina of the dorsal horn in morphinetreated animals. Morphine-induced hyperalgesia was reversed by spinal administration of an NK-1 receptor antagonist in rats and mice, and was observed in wildtype (NK-1 +/+ ), but not NK-1 receptor knockout (NK-1 −/− ), mice. These data support a critical role for the NK-1 receptor in the expression of sustained morphine-induced hyperalgesia. Additionally, these data indicate that sustained opiate administration induces changes reminiscent of those associated with inflammatory pain. These opiate-induced changes might produce unintended deleterious actions in the course of pain treatment in patients. Understanding of sustained morphine-induced neurochemical changes will help identify approaches that limit the deleterious actions of opiates.

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Inhibition of inflammation and hyperalgesia in NK-1 receptor knock-out mice

Cited by 24 publications

References 13 publications

Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

Involvement of transient receptor potential vanilloid 1 in the vascular and hyperalgesic components of joint inflammation

Enhanced Immunoglobulin A Response and Protection againstSalmonella entericaSerovar Typhimurium in the Absence of the Substance P Receptor

Role of NK-1 neurotransmission in opioid-induced hyperalgesia

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