Post-injury administration of minocycline: An effective treatment for nerve-injury induced neuropathic pain

Mei, Xiao Peng; Xu, Hao; Xie, Congying; Ren, Jun; Zhou, Yang; Zhang, Hui; Xu, Li

doi:10.1016/j.neures.2011.03.012

Cited by 69 publications

(46 citation statements)

References 34 publications

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“…It is probable that the minocycline could not inhibit the microglia because it was not activated. In previous studies, IT minocycline did reveal inhibitory effects of microglia which was activated in cancer [6] and neuropathic [13] pain models with the same doses used in the present study, suggesting the dose of minocycline used in the present study could be enough if microglia was activated. However, further studies are necessary to resolve this uncertainty.…”

Section: Discussionsupporting

confidence: 69%

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Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia

et al. 2016

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Background: Brain-derived neurotrophic factor (BDNF) from spinal microglia is crucial for aberrant nociceptive signaling in several pathological pain conditions, including postoperative pain. We assess the contribution of spinal microglial activation and associated BDNF overexpression to the early post-incisional nociceptive threshold. Methods: Male Sprague-Dawley rats were implanted with an intrathecal catheter. A postoperative pain model was established by plantar incision. Thermal and mechanical nociceptive responses were assessed by infrared radiant heat and von Frey filaments before and after plantar incision. Rats were injected intrathecally the microglial activation inhibitor minocycline before incision, 24 h after incision, or both. Other groups were subjected to the same treatments and the L4-L5 spinal cord segment removed for immunohistochemical analysis of microglia activation and BNDF expression. Results: Plantar incision reduced both thermal latency and mechanical threshold, indicating thermal hypersensitivity and mechanical allodynia. Minocycline temporally reduced thermal withdrawal latency but had no effect on mechanical withdrawal threshold, spinal microglial activity, or dorsal horn BDNF overexpression during the early post-incision period. Conclusion: These results suggest that spinal microglia does not contribute substantially to post-incisional nociceptive threshold. The BDNF overexpression response that may contribute to postoperative hyperalgesia and allodynia is likely derived from other sources.

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Section: Discussionsupporting

confidence: 69%

“…The dose of minocycline chosen was based on previous studies [6,13]. , All injections were followed by a flush of 10 μl normal saline.…”

Section: Drugsmentioning

confidence: 99%

Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia

et al. 2016

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“…Previous reports indicate that minocycline could generate antinociceptive effects on neuropathic pain induced by peripheral nerve injury, inflammation or spinal cord injury [11,39,40,41]. Moreover, a previous study confirmed that intrathecal minocycline was effective for the treatment of SNL-induced neuropathic pain even after the established pain model [42]. The therapeutic time window for intrathecal minocycline is the initiation period (no more than 1 week) of peripheral nerve injury-induced neuropathic pain.…”

Section: Discussionmentioning

confidence: 94%

Combination of Tramadol with Minocycline Exerted Synergistic Effects on a Rat Model of Nerve Injury-Induced Neuropathic Pain

et al. 2013

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Neuropathic pain is a refractory clinical problem. Certain drugs, such as tramadol, proved useful for the treatment of neuropathic pain by inhibiting the activity of nociceptive neurons. Moreover, studies indicated that suppression or modulation of glial activation could prevent or reverse neuropathic pain, for example with the microglia inhibitor minocycline. However, few present clinical therapeutics focused on both neuronal and glial participation when treating neuropathic pain. Therefore, the present study hypothesized that combination of tramadol with minocycline as neuronal and glial activation inhibitor may exert some synergistic effects on spinal nerve ligation (SNL)-induced neuropathic pain. Intrathecal tramadol or minocycline relieved SNL-induced mechanical allodynia in a dose-dependent manner. SNL-induced spinal dorsal horn Fos or OX42 expression was downregulated by intrathecal tramadol or minocycline. Combination of tramadol with minocycline exerted powerful and synergistic effects on SNL-induced neuropathic pain also in a dose-dependent manner. Moreover, the drug combination enhanced the suppression effects on SNL-induced spinal dorsal horn Fos and OX42 expression, compared to either drug administered alone. These results indicated that combination of tramadol with minocycline could exert synergistic effects on peripheral nerve injury-induced neuropathic pain; thus, a new strategy for treating neuropathic pain by breaking the interaction between neurons and glia bilaterally was also proposed.

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“…However, no effect on existing mechanical allodynia and thermal hyperalgesia were observed in this study when the treatment was started from day 5 post-ligation up to day 10. More recent data shows that antiallodynic effect can be observed if the treatment (intrathecal injection) is applied 1, 3, 7 days after nerve ligation, but not 10 or 21 days after (Mei et al 2011). Taken together, these results clearly show that there is short time window for a possible therapeutic intervention.…”

Section: Antihypernociceptive Effectsmentioning

confidence: 68%

“…Treatments available to date are based on the empirical use of old unconventional drugs (Dray 2008). In this context, minocycline has been undergoing preclinical studies (Raghavendra et al 2003;Ledeboer et al 2005;Mei et al 2011;Morgado et al 2011). Ledeboer et al (2005) showed that intrathecal minocycline prevents mechanical allodynia induced by perisciatic administration of zymosan or that induced by spinal immune activation after intrathecal injection of gp120 from human immunodeficiency virus (HIV)-1.…”

Section: Antihypernociceptive Effectsmentioning

confidence: 99%

Tetracyclines and pain

Bastos

Oliveira

Watkins

et al. 2012

Naunyn-Schmiedeberg's Arch Pharmacol

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Tetracyclines are natural or semi-synthetic bacteriostatic agents which have been used since late 1940s against a wide range of gram-positive and gram-negative bacteria and atypical organisms such as chlamydia, mycoplasmas, rickettsia, and protozoan parasites. After the discovery of the first tetracyclines, a second generation of compounds was sought in order to improve water solubility for parenteral administration or to enhance bioavailability after oral administration. This approach resulted in the development of doxycycline and minocycline in the 1970s. Doxycycline was included in the World Health Organization Model List of Essential Medicines either as antibacterial or to prevent malaria or to treat patients with this disease. Additional development led to the third generation of tetracyclines, being tigecycline the only medicine of this class to date. Besides antibacterial activities, the anti-inflammatory, antihypernociceptive and neuroprotective activities of tetracyclines began to be widely studied in the late 1990s. Indeed, there has been an increasing interest in investigating the effects induced by minocycline as this liposoluble derivative is known to cross the blood-brain barrier to the greatest extent. Minocycline induces antihypernociceptive effects in a wide range of animal models of nociceptive, inflammatory and neuropathic pain. In this study, we discuss the antihypernociceptive activity of tetracyclines and summarise its underlying cellular and molecular mechanisms.

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Post-injury administration of minocycline: An effective treatment for nerve-injury induced neuropathic pain

Cited by 69 publications

References 34 publications

Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia

Early Postoperative Nociceptive Threshold and Production of Brain-Derived Neurotrophic Factor Induced by Plantar Incision Are Not Influenced with Minocycline in a Rat: Role of Spinal Microglia

Combination of Tramadol with Minocycline Exerted Synergistic Effects on a Rat Model of Nerve Injury-Induced Neuropathic Pain

Tetracyclines and pain

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