The Effect of Morphine on Glial Cells as a Potential Therapeutic Target for Pharmacological Development of Analgesic Drugs

Hameed, Haroon; Hameed, Mariam; Christo, Paul J.

doi:10.1007/s11916-010-0093-y

Cited by 30 publications

(26 citation statements)

References 58 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have shown that opioid receptors are [3,32,33] . After chronic or acute exposure to morphine, activated neurons and glia exhibit increased expression of pro-infl ammatory cytokines, such as TNF-α, IL-1β, IL-6 [19,34,35] , and chemokines [36,37] .…”

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats

et al. 2014

View full text Add to dashboard Cite

Nuclear factor kappa B (NF-κB) in the spinal cord is involved in pro-infl ammatory cytokine-mediated pain facilitation. However, the role of NF-κB activation in chronic morphine-induced analgesic tolerance and the underlying mechanisms remain unclear. In the present study, we found that the level of phosphorylated NF-κB p65 (p-p65) was increased in the dorsal horn of the lumbar 4-6 segments after intrathecal administration of morphine for 7 consecutive days, and the p-p65 was co-localized with neurons and astrocytes. The expression of TNF-α and IL-1β was also increased in the same area. In addition, pretreatment with pyrrolidinedithiocarbamate (PDTC) or SN50, inhibitors of NF-κB, prevented the development of morphine analgesic tolerance and alleviated morphine withdrawal-induced allodynia and hyperalgesia. The increase in TNF-α and IL-1β expression induced by chronic morphine exposure was also partially blocked by PDTC pretreatment. In another experiment, rats receiving PDTC or SN50 beginning on day 7 of morphine injection showed partial recovery of the anti-nociceptive effects of morphine and attenuation of the withdrawal-induced abnormal pain. Meanwhile, intrathecal pretreatment with lipopolysaccharide from Rhodobacter sphae roides, an antagonist of toll-like receptor 4 (TLR4), blocked the activation of NF-κB, and prevented the development of morphine tolerance and withdrawalinduced abnormal pain. These data indicated that TLR4-mediated NF-κB activation in the spinal cord is involved in the development and maintenance of morphine analgesic tolerance and withdrawalinduced pain hypersensitivity.

show abstract

Section: Discussionmentioning

confidence: 99%

Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Maybe not -it may be able to block the gap junctions of inhibitory interneuron by itself. Glial cells can be inhibited by opioids, because they have opioid receptors (31), and glial cells are also connected by gap junctions (23), so it is probable that a proportion of morphine analgesia arises through inhibition of interconnected glial cells and reduction of the release of their inflammatory mediators (31); in such circumstances carbenoxolone would inhibit the glial cell gap junctions; in other words, carbenoxolone inhibits glial cell inhibition produced by morphine, thus alleviating morphine analgesia. By itself, carbenoxolone can inhibit glial cell gap junctions, but in this state, carbenoxolone inhibits glial cell activity, reducing the release of inflammatory mediators by glial cells and producing analgesia; these hypotheses also require further investigation.…”

Section: Gap Junctions' Role In Morphine Analgesiamentioning

confidence: 99%

Effects of Intrathecal Carbenoxolone Treatment on Nociception and Analgesia in Rat

Kamalpour¹,

Fereidoni²,

Moghimi³

2014

Balkan Med J

View full text Add to dashboard Cite

Background: Gap junctions (GJ) are important in pain signalling at the spinal cord level. Aims: The aim of this investigation was to study the effects of GJ on nociception and the analgesic/hyperalgesic effects of mor phine following administration of carbenoxolone as a GJ blocker. Male Wistar rats (200-250 g) were divided into three groups: saline i.p., 10 mg/kg and 1 μg/kg i.p. morphine, each with two subgroups. One was treated intrathecally with saline and the other with carben oxolone. Study Design: Animal experiment. Methods: The thermal nociception threshold was measured prior to and after injections using the tail flick test. Chemical nociception assessment was conducted using a 0.05-mL subplantar injection of 2.5% formalin. Results: Both formalin-induced neurogenic and inflammatory nociception were reduced in the [saline i.p./carbenoxolone i.t.] and [morphine 1 µg/kg, i.p./carbenoxolone i.t.] subgroups (p<0.001). The 10 mg/kg i.p. morphine, i.t./carbenoxolone treatment reduced morphineinduced analgesia in the inflammatory phase (p<0.05), while it was ineffective in the neurogenic phase. Carbenoxolone decreased 1 µg/ kg i.p. morphine-induced hyperalgesia in the tail flick test (p<0.001). Conclusion: Based on the results, GJ probably play a role in nociception at the spinal cord level. This may be due to the facilitation of inflammatory mediators released from glial cells or the connection between stimulatory interneurons and projection neurons. GJ blocking attenuated morphine-induced analgesia. This may be due to the attenuation of pre/post-synaptic inhibitory effects of morphine at the spinal cord level. As demonstrated by the investigations, GJ are present between inhibitory interneurons. Therefore, we can assume that blockage of GJ between inhibitory interneurons will reduce morphine-induced analgesia at the spinal cord level. However, this requires further investigation. (Balkan Med J 2014;31:164-72).

show abstract

“…However, opioids are reported to have suboptimal therapeutic efficacy against neuropathic pain (Bleeker et al, 2001;Cherny et al, 1994). There have been reports that chronic morphine treatment leading to 'morphine tolerance' may indeed induce the death of neurons (Hameed et al, 2010;Mao et al, 2002). The ineffectiveness of morphine in the context of neuropathic pain may be due to the reduced number of presynaptic opioid receptors due to the degeneration of primary afferent neurons, which is in turn caused by nerve damage.…”

Section: Opioid Tolerance In Neuropathic Painmentioning

confidence: 99%

Neural - Glial Interaction in Neuropathic Pain

Manaheji¹

2012

Basic Principles of Peripheral Nerve Disorders

View full text Add to dashboard Cite

The Effect of Morphine on Glial Cells as a Potential Therapeutic Target for Pharmacological Development of Analgesic Drugs

Cited by 30 publications

References 58 publications

Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats

Toll-like receptor 4-mediated nuclear factor-κB activation in spinal cord contributes to chronic morphine-induced analgesic tolerance and hyperalgesia in rats

Effects of Intrathecal Carbenoxolone Treatment on Nociception and Analgesia in Rat

Neural - Glial Interaction in Neuropathic Pain

Contact Info

Product

Resources

About