Characterization of the hyperalgesic effect induced by intrathecal injection of substance P

Matsumura, Hisao; Sakurada, Tsukasa; Hara, Akiyoshi; Sakurada, Shinobu; Kisara, Kensuke

doi:10.1016/0028-3908(85)90027-9

Cited by 85 publications

(11 citation statements)

References 54 publications

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“…For comparison, intrathecal administration of substance P 100 nmol significantly produced pronociceptive/hyperalgesic effects, manifested as reduced tail-withdrawal latencies in 46°C water. These results agree with rodent studies, indicating that intrathecal substance P causes hyperalgesic effects 27,30. Intrathecal administration of substance P and N/OFQ both produced a similar degree of hyperalgesic effects, as shown by decreased response latency approximately for 2 to 3 seconds in rodents 30,39.…”

Section: Discussionsupporting

confidence: 90%

Antinociceptive Effects of Nociceptin/Orphanin FQ Administered Intrathecally in Monkeys

Naughton

2009

The Journal of Pain

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Nociceptin/orphanin FQ (N/OFQ) is the endogenous peptide for the NOP receptors. Depending on the doses, intrathecal administration of N/OFQ has dual actions (ie, hyperalgesia and antinociception) in rodents. However, the pharmacological profile of intrathecal N/OFQ is not fully known in primates. The aim of this study was to investigate behavioral effects of intrathecal N/OFQ over a wide dose range and to compare its effects with ligands known to produce hyperalgesia or antinociception in monkeys. Intrathecal N/OFQ from 1 fmol to 1 nmol did not produce any hyperalgesic or scratching responses. In contrast, intrathecal substance P 100 nmol produced hyperalgesia, and intrathecal DAMGO 10 nmol produced antinociception. At the dose range between 10 nmol and 1 µmol, intrathecal N/OFQ dose-dependently produced thermal antinociception against a noxious stimulus in 2 intensities. More importantly, N/OFQ in combined with intrathecal morphine dose-dependently potentiated morphine-induced antinociception without inhibiting morphineinduced itch/scratching. Taken together, this study is the first to provide a unique functional profile of intrathecal N/OFQ over a wide dose range in primates. Intrathecal N/OFQ produces thermal antinociception without anti-morphine actions or scratching responses, indicating that N/OFQ or NOP receptor agonists represent a promising target as spinal analgesics.Perspective: Intrathecal administration of N/OFQ only produced thermal antinociception, not hyperalgesia, in monkeys. In addition, intrathecal N/OFQ does not have anti-morphine actions or itch/scratching responses. This study strongly supports the therapeutic potential of N/OFQ or NOP receptor agonists as spinal analgesics for clinical trials. KeywordsSpinal cord; analgesia; NOP receptors; substance P; thermal hyperalgesia Spinal administration of µ-opioid receptor agonists is an important method for pain management, and it is widely used for obstetric analgesia. 8,10 However, itch/pruritus is the most common side effect derived from spinal opioids, and it reduces the value of pain relief afforded by spinal opioids. 8 Therefore, the aim of this study was to extensively investigate and directly compare the behavioral effects of intrathecally administered N/OFQ over a wide dose range in monkeys.As noted, rodent studies have shown that intrathecal DAMGO and substance P produced antinociceptive and pronociceptive effects, respectively. 29,30,41 By using both behavioral end points (ie, antinociception/hyperalgesia and scratching responses), effects of intrathecal DAMGO and substance P were compared with those of intrathecal N/OFQ. Antinociceptive effects of intrathecal N/OFQ were further studied against a noxious stimulus in 2 intensities. In addition, the potential interaction between intrathecal N/OFQ and morphine was determined to explore whether N/OFQ modulated intrathecal morphine-induced antinociception and scratching responses. Materials and Methods SubjectsEighteen adult intact male and female rhesus monkeys (Macacamulatta) with...

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Section: Discussionsupporting

confidence: 90%

Antinociceptive Effects of Nociceptin/Orphanin FQ Administered Intrathecally in Monkeys

Naughton

2009

The Journal of Pain

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“…Moreover, the electrical stimulation of thin, unmyelinated afferent (C-) fibres (Go and Yaksh, 1987;Brodin et al, 1987;Klein et al, 1992) or the administration of capsaicin (Go and Yaksh, 1987;Takano et al, 1993) have each been found to result in the release of substance P. Further evidence that substance P acts as a neurotransmitter for pain is that NK1 receptor antagonists block the responses of spinal cord neurons elicited by the different noxious stimuli (Snider et al, 1991;Radhakrishnan and Henry, 1991). Moreover, the intrathecal administration of substance P was found to induce pain behaviour in animals (Piercey et al, 1981;Hylden and Wilcox, 1983;Matsamura et al, 1985).…”

Section: Substance P: Neurotransmitter or Neuromodulator?mentioning

confidence: 99%

Substance P

Snijdelaar¹,

Dirksen

Slappendel

et al. 2000

European Journal of Pain

119

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“…Substance P, an undecapeptide, is widely distributed in the brain (Hokfelt et al 1978). It is a potent vasodepressor agent when injected intravenously (Maggi et al 1985) and causes a hyperalgesic effect given intrathecally (Matsumura et al 1985). However, it is still not clear whether captopril does interfere with substance P metabolism.…”

Section: Introductionmentioning

confidence: 99%

Captopril Does Not Potentiate Hypotension and Algesia by Substance P

Hui

Ogle

1986

Clin Exp Pharma Physio

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Captopril (1-5 mg/kg, i.v.) did not affect the vasodepressor responses to substance P (1-30 micrograms/kg, i.v.) in anaesthetized rats. Substance P (100 micrograms/kg, s.c.) produced significant algesia in mice; this was not potentiated by the smaller doses of captopril (1-2 mg/kg, i.p.), but was instead antagonized by the high dose (5 mg/kg, i.p.). It is concluded that captopril does not have any influence on substance P degradation in vivo since the pharmacological actions of the undecapeptide are not enhanced after captopril treatment.

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Characterization of the hyperalgesic effect induced by intrathecal injection of substance P

Cited by 85 publications

References 54 publications

Antinociceptive Effects of Nociceptin/Orphanin FQ Administered Intrathecally in Monkeys

Antinociceptive Effects of Nociceptin/Orphanin FQ Administered Intrathecally in Monkeys

Substance P

Captopril Does Not Potentiate Hypotension and Algesia by Substance P

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