Effects of Morphine on Oedema and Tissue Concentration of Nerve Growth Factor in Experimental Inflammation of the Rat Paw

Amann, Rainer; Lanz, Ilse; Schuligoi, Rufina

doi:10.1159/000063800

Cited by 18 publications

(15 citation statements)

References 21 publications

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“…Previous evidence showed a negative interaction between opiates and NGF signaling pathways in primary sensory neurons (34). Conversely, the inflammation-related increase of NGF induced by carrageenan is attenuated by morphine (35). Morphine and other opiates are currently used as analgesics for several types of severe persistent pain, although their use is limited by several drawbacks, including development of tolerance and physical dependence (49).…”

Section: Discussionmentioning

confidence: 99%

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The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

Ugolini¹,

Marinelli

Covaceuszach

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

114

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Nerve growth factor (NGF) is involved in pain transduction mechanisms and plays a key role in many persistent pain states, notably those associated with inflammation. On this basis, both the NGF ligand and its receptor TrkA (tyrosine kinase A) represent an eligible target for pain therapy. Although the direct involvement of NGF in pain modulation is well established, the effect of a direct functional block of the TrkA receptor is still unknown. In this study, we have demonstrated that MNAC13, the only anti-TrkA monoclonal antibody for which function neutralizing properties have been clearly shown both in vitro and in vivo, induces analgesia in both inflammatory and neuropathic pain models, with a surprisingly long-lasting effect in the latter. The formalin-evoked pain licking responses are significantly reduced by the MNAC13 antibody in CD1 mice. Remarkably, treatment with the anti-TrkA antibody also produces a significant antiallodynic effect on neuropathic pain: repeated i.p. injections of MNAC13 induce significant functional recovery in mice subjected to sciatic nerve ligation, with effects persisting after administration. Furthermore, a clear synergistic effect is observed when MNAC13 is administered in combination with opioids, at doses that are not efficacious per se. This study represents a direct demonstration that neutralizing antibodies directed against the TrkA receptor may display potent analgesic effects in inflammatory and chronic pain.analgesia ͉ behavior ͉ mice ͉ nerve growth factor

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Section: Discussionmentioning

confidence: 99%

“…In addition, because a functional interaction between NGF and opioid system was reported in experimental models of inflammatory pain (34,35), the possible synergistic effects of the anti-TrkA antibody with opiates, such as morphine and fentanyl, were investigated.…”

mentioning

confidence: 99%

The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

Ugolini¹,

Marinelli

Covaceuszach

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

114

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“…The receptors have also been implicated in the inflammatory process; systemically administered morphine reduces edema and plasma extravasation with an unknown mechanism of action (Hargreaves et al, 1988;Joris et al, 1990;Sacerdote et al, 1996;Walker et al, 1996;Alebouyeh et al, 2002;Amann et al, 2002). In the current study, we sought to investigate the role of centrally and/or peripherally located receptors in pain and edema caused by acute inflammation.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have demonstrated that systemically administered morphine produces a substantial reduction of inflammagen-induced extravasation (Hargreaves et al, 1988;Joris et al, 1990) and edema (Hargreaves et al, 1988;Joris et al, 1990;Sacerdote et al, 1996;Walker et al, 1996;Alebouyeh et al, 2002;Amann et al, 2002). Furthermore, Sacerdote et al (1996) and Planas et al (1995) observed a proinflammatory effect of the opioid antagonists naltrexone and naloxone, respectively.…”

mentioning

confidence: 99%

The Role of Central and Peripheral μ Opioid Receptors in Inflammatory Pain and Edema: A Study Using Morphine and DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl]-acetic Acid)

Whiteside

Boulet²,

Walker³

2005

The Journal of Pharmacology and Experimental Therapeutics

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The role of opioid receptors located in the central nervous system (CNS) and peripheral nervous system in inflammatory pain is well established. In contrast, although it is has been shown that agonists can reduce other manifestations of inflammation, such as edema, the mechanism of action remains unclear. In this study, we have activated receptors located centrally, those located peripherally, and those located both centrally and peripherally and compared the effects on pain and edema using the rat carrageenan model of acute inflammation. Activation of receptors located only in the periphery, by administration of the peripheralized agonist [8-(3,3-diphenylpropyl)-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl]-acetic acid (DiPOA) or local administration of morphine, resulted in antihyperalgesia (30 mg/kg DiPOA, 83% inhibition; 100 g/rat morphine, 75% inhibition) without affecting edema. In contrast, activation of both central and peripheral receptors using systemically administered morphine resulted in antihyperalgesia (1 mg/kg, 80% inhibition) and inhibition of edema (10 mg/kg, 54% inhibition). Finally, activation of only receptors located in the CNS, by central administration of DiPOA or systemic administration of morphine after block of only the peripheral receptors using q-naltrexone, resulted in a significant reduction in edema. Our findings confirm the role of peripheral receptors in the pathology of pain associated with acute inflammation and argue against the involvement of these receptors in edema formation. Furthermore, our data demonstrate that activation of receptors in the brain inhibits carrageenan-induced edema and suggest that the antiedematous effect of morphine is due to action at central receptors alone.

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“…For example, early reports demonstrated that NGF could reverse edema caused by the injection of carrageenin, serotonin and dextran (Banks et al 1984;Amico-Roxas et al 1989). Later authors called into question this relationship in inflamed skin (Koltzenburg et al 1999;Amann et al 2002). Finally, the injection of NGF into unperturbed skin has been observed to cause rather than reduce edema (Schuligoi and Amann 1998).…”

Section: Introductionmentioning

confidence: 99%

Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional pain syndrome type I

Sabsovich

Wei

Guo

et al. 2008

Pain

108

126

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Effects of Morphine on Oedema and Tissue Concentration of Nerve Growth Factor in Experimental Inflammation of the Rat Paw

Cited by 18 publications

References 21 publications

The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

The function neutralizing anti-TrkA antibody MNAC13 reduces inflammatory and neuropathic pain

The Role of Central and Peripheral μ Opioid Receptors in Inflammatory Pain and Edema: A Study Using Morphine and DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl]-acetic Acid)

Effect of anti-NGF antibodies in a rat tibia fracture model of complex regional pain syndrome type I

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