An isobolographic analysis of the effects of N‐methyl‐D‐aspartate and NK<sub>1</sub> tachykinin receptor antagonists on inflammatory hyperalgesia in the rat

Ren, Ke; Iadarola, Michael J.; Dubner, Ronald

doi:10.1111/j.1476-5381.1996.tb15174.x

Cited by 39 publications

(16 citation statements)

References 61 publications

(102 reference statements)

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“…These data suggest that an SP-mediated thermal allodynia does not develop in the setting of inflammation. Although this conclusion is somewhat at odds with the study of Ren et al (1996), which reported that NK-1 antagonists attenuate hyperalgesia to thermal stimulation in CFA-treated rats, it is consistent with the report of Liu and Sandkühler (1995), which found enhanced responses of lamina I neurons to mechanical, but not to thermal, skin stimuli during superfusion with SP.…”

Section: Nk-1 Receptor Internalization In the Setting Of Inflammationsupporting

confidence: 87%

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

et al. 1997

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Although the neurokinin-1 (NK-1)/substance P (SP) receptor is expressed by neurons throughout the spinal dorsal horn, noxious chemical stimulation in the normal rat only induces internalization of the receptor in cell bodies and dendrites of lamina I. Here we compared the effects of mechanical and thermal stimulation in normal rats and in rats with persistent hindpaw inflammation. Electron microscopic analysis confirmed the upregulation of receptor that occurs with inflammation and demonstrated that in the absence of superimposed stimulation, the increased receptor was, as in normal rats, concentrated on the plasma membrane. In general, noxious mechanical was more effective than noxious thermal stimulation in inducing NK-1 receptor internalization, and this was increased in the setting of inflammation. Although a 5 sec noxious mechanical stimulus only induced internalization in 22% of lamina I neurons in normal rats, after inflammation, it evoked near-maximal (98%) internalization in lamina I, produced significant changes in laminae III-VI, and expanded the rostrocaudal distribution of neurons with internalized receptor. Even non-noxious (brush) stimulation of the inflamed hindpaw induced internalization in large numbers of superficial and deep neurons. For thermal stimulation, the percentage of cells with internalized receptor increased linearly at Ͼ45°C, but in normal rats, these were restricted to lamina I. After inflammation, however, the 52°C stimulus also induced internalization in 25% of laminae III-IV cells. These studies provide a new perspective on the reorganization of dorsal horn circuits in the setting of persistent injury and demonstrate a critical contribution of SP.

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Section: Nk-1 Receptor Internalization In the Setting Of Inflammationsupporting

confidence: 87%

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

et al. 1997

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“…In addition, thermal hyperalgesia in rats or mice with rheumatoid arthritis has been reported by others (Andrew and Greenspan, 1999;Ren et al, 1996;Inglis et al, 2007a,b). However, thermal hyperalgesia was not observed in PIA rats.…”

Section: Discussionmentioning

confidence: 83%

Mechanical hyperalgesia is attenuated by local administration of octreotide in pristane-induced arthritis in Dark-Agouti rats

Yao

Guo

et al. 2008

Life Sciences

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“…Moreover, increased distribution of neurons showing NK-1 receptor internalization was observed following noxious stimulation, with noxious stimulation induced NK-1 receptor internalization in deep dorsal horn neurons, instead of only in lamina I neurons as observed in untreated controls (Abbadie et al, 1997). 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).…”

Section: Discussionmentioning

confidence: 92%

Role of NK-1 neurotransmission in opioid-induced hyperalgesia

King

Gardell

Wang

et al. 2005

Pain

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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An isobolographic analysis of the effects of N‐methyl‐D‐aspartate and NK₁ tachykinin receptor antagonists on inflammatory hyperalgesia in the rat

Abstract: 1The interaction between N-methyl-D-aspartate (NMDA)

Cited by 39 publications

References 61 publications

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

Mechanical hyperalgesia is attenuated by local administration of octreotide in pristane-induced arthritis in Dark-Agouti rats

Role of NK-1 neurotransmission in opioid-induced hyperalgesia

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An isobolographic analysis of the effects of N‐methyl‐D‐aspartate and NK1 tachykinin receptor antagonists on inflammatory hyperalgesia in the rat

Abstract: 1The interaction between N-methyl-D-aspartate (NMDA)

Cited by 39 publications

References 61 publications

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

Inflammation Increases the Distribution of Dorsal Horn Neurons That Internalize the Neurokinin-1 Receptor in Response to Noxious and Non-Noxious Stimulation

Mechanical hyperalgesia is attenuated by local administration of octreotide in pristane-induced arthritis in Dark-Agouti rats

Role of NK-1 neurotransmission in opioid-induced hyperalgesia

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An isobolographic analysis of the effects of N‐methyl‐D‐aspartate and NK₁ tachykinin receptor antagonists on inflammatory hyperalgesia in the rat