Role of μ-opioid receptors in formalin-induced pain behavior in mice

Zhao, Cheng; Tao, Yuan Xiang; Tall, Jill M.; Donovan, David M.; Meyer, Richard A.; Raja, Srinivasa N.

doi:10.1016/s0014-4886(03)00346-7

Cited by 27 publications

(17 citation statements)

References 38 publications

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“…2). MOR Ϫ/Ϫ mice showed a similar degree of nocifensive behavior as wild-type mice during the first phase of Formalin-induced pain, which primarily results from a direct activation of nociceptive afferents (Zhao et al, 2003). Furthermore, neither naloxone (intraperitoneally) nor CTOP (D-Phe-Cys-Tyr-D-Trp-Orn-ThrPen-Thr-NH 2 ) (intrathecally) affected the initiation and magnitude of pain behavior in this phase (Wu et al, 2002;Zhao et al, 2003).…”

Section: Discussionmentioning

confidence: 91%

“…In fact, an increase in spinal nociceptive reflex was more evident in the MOR Ϫ/Ϫ mice than that in wild-type mice after peripheral nerve injury (Mansikka et al, 2004). The second phase of Formalin-induced pain, which recruits spinal sensitization, was also significantly potentiated in MOR Ϫ/Ϫ mice (Sugimoto et al, 1986;Zhao et al, 2003) and in wild-type mice after pretreatment with MOR antagonists (Zhao et al, 2003). Naloxone also induced a dose-dependent increase in windup like phenomenon in withdrawal reflexes (Hartell and Headley, 1991;Ramos-Zepeda and Herrero, 2005).…”

Section: Discussionmentioning

confidence: 95%

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Windup in Dorsal Horn Neurons Is Modulated by Endogenous Spinal μ-Opioid Mechanisms

Guan¹,

Borzan²,

Meyer³

et al. 2006

J. Neurosci.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 95%

Windup in Dorsal Horn Neurons Is Modulated by Endogenous Spinal μ-Opioid Mechanisms

Guan¹,

Borzan²,

Meyer³

et al. 2006

J. Neurosci.

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“…The decreased antinociceptive effect of morphine in the formalin test produced by Derm-sap further supports the generality of the previous conclusion from hotplate data that dorsal horn MOR-expressing neurons play an important role in the antinociceptive action of systemic morphine. Transgenic mice lacking MOR expression have been reported to have some abnormalities of nocifensive behavior (increased interphase or phase II behavior) in the formalin test (Martin et al, 2003;Zhao et al, 2003), and so have mice with defective postsynaptic signaling by the MOR receptor because of lack of expression of GIRK2 (Mitrovic et al, 2003). Mice lacking GIRK2 also show decreased morphine effect in the formalin test.…”

Section: Discussionmentioning

confidence: 99%

Spinal μ-Opioid Receptor-Expressing Dorsal Horn Neurons: Role in Nociception and Morphine Antinociception

Kline¹,

Wiley²

2008

J. Neurosci.

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The role of spinal cord -opioid receptor (MOR)-expressing dorsal horn neurons in nociception and morphine analgesia is incompletely understood. Using intrathecal dermorphin-saporin (Derm-sap) to selectively destroy MOR-expressing dorsal horn neurons, we sought to determine the role of these neurons in (1) normal baseline reflex nocifensive responses to noxious thermal stimulation (hotplate, tail flick) and to persistent noxious chemical stimulation (formalin) and (2) the antinociceptive activity of intrathecal and systemic morphine in the same tests. Lumbar intrathecal Derm-sap (500 ng) produced (1) partial loss of lamina II MOR-expressing dorsal horn neurons, (2) no effect on MOR-expressing dorsal root ganglion neurons, and (3) no change in baseline tail-flick and hotplate reflex nocifensive responses. Derm-sap treatment attenuated the antinociceptive action of both intrathecal and systemic morphine on hotplate responses. Derm-sap treatment had two effects in the formalin test: (1) increased baseline nocifensive responding and (2) reduced antinociceptive action of systemic morphine. We conclude that MOR-expressing dorsal horn neurons (1) are not essential for determining nocifensive reflex responsiveness to noxious thermal stimuli, (2) are necessary for full antinociceptive action of morphine (intrathecal or systemic) in these tests, and (3) play a significant role in the endogenous modulation of reflex nocifensive responses to persistent pain in the formalin test. Thus, one would predict that altering the activity of MOR-expressing dorsal horn neurons would be antinociceptive and of interest in the search for new approaches to management of chronic pain.

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“…Opioid analgesics however, are capable of inhibiting the early and late phases of the formalin-induced pain (Vasudevan et al, 2007). In this study, C. Platythyrsa significantly inhibited both phases of the formalin test suggested that this extract may have an endogenous opioid-like analgesic activity on µ-opioid receptors which are tonically activated by formalin injection (Zhao et al, 2003) as well as anti-inflammatory properties. Carrageenan-induced inflammation occurs in two phases: the early phase which occurs between 1 to 2 h after injection of the phlogistic agent is mediated by the release of histamine, serotonin and bradykinin; while the late phase which may last for up to 6 h after carrageenan injection involves the active release of TNF-alpha, IL 1beta, COX-2 and prostaglandins which tend to worsen the inflammatory reaction (Gupta et al, 2006;Loram et al, 2007).…”

Section: Discussionmentioning

confidence: 51%

The effect of Cordia platythyrsa on various experimental models of pain and carrageenan induced inflammation

Nkeh-Chungag

Ndebia²,

Mbafor³

et al. 2014

Afr. J. Biotechnol.

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Only one study has reported on the medicinal properties of Cordia platythyrsa (C. platythyrsa) though it is used in African traditional medicine for treatment of fever and pain. The current study aimed at investigating the analgesic and anti-inflammatory properties of C. platythyrsa using various animal models: writhing test, tail flick, thermal hyperalgesia, mechanically induced-pain, formalin-induced pain and carrageenan-induced inflammation tests. Like aspirin, the two doses of plant extracts used inhibited acetic acid-induced pain though these effects were weaker than the effects of morphine. Although, the plant extract significantly (p<0.01) inhibited thermal pain, its effects were less significant compared to morphine. Celecoxib (10 mg/kg) and plant extract (100 mg/kg) significantly inhibited thermal hyperalgesia compared to indomethacin. On the other hand, both doses of plant extract significantly increased mechanical pain thresholds 30 and 90 min post treatment. The plant extract (150 mg/kg) inhibited both the neurogenic and inflammatory pain phases of formalin-induced pain as well as carrageenan-induced inflammation. This study is the first to show that C. platythyrsa has analgesic and anti-inflammatory properties.

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Role of μ-opioid receptors in formalin-induced pain behavior in mice

Cited by 27 publications

References 38 publications

Windup in Dorsal Horn Neurons Is Modulated by Endogenous Spinal μ-Opioid Mechanisms

Windup in Dorsal Horn Neurons Is Modulated by Endogenous Spinal μ-Opioid Mechanisms

Spinal μ-Opioid Receptor-Expressing Dorsal Horn Neurons: Role in Nociception and Morphine Antinociception

The effect of Cordia platythyrsa on various experimental models of pain and carrageenan induced inflammation

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