Effects of minocycline on Na+ currents in rat dorsal root ganglion neurons

Kim, Tae Hoon; Kim, Hong Im; Kim, Jungho; Park, Mijung; Song, Jin-Ho

doi:10.1016/j.brainres.2010.11.038

Cited by 34 publications

(27 citation statements)

References 57 publications

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“…Moreover, minocycline is known to exert its effects not only on microglia but other cell types including neurons. For example, minocycline inhibited Na + currents in DRG neurons, resulting antinociceptive effets [22]. It is possible that the inhibitory effects of minocycline on DRG neurons could contribute the transient antinociceptive effects of minocycline observed in the present study.…”

Section: Discussionmentioning

confidence: 61%

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: Discussionmentioning

confidence: 61%

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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“…Nevertheless, minocycline also possesses neuroprotective roles [20,28,45,46] . One notable characteristic of minocycline is that it has a direct effect on sodium channels in primary afferent neurons [47] , which suggests it has a role of peripheral analgesia. Based on these previous findings, we designed the present study to identify the effects of minocycline on spinal astrocytes at a later stage (from d 14 to d 16) of BCP.…”

Section: Bcp Induced By Walker 256 Mammary Carcinoma Cell Inocula Tionmentioning

confidence: 99%

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

et al. 2016

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Aim: To investigate the mechanisms underlying the anti-nociceptive effect of minocycline on bone cancer pain (BCP) in rats.Methods: A rat model of BCP was established by inoculating Walker 256 mammary carcinoma cells into tibial medullary canal. Two weeks later, the rats were injected with minocycline (50, 100 μg, intrathecally; or 40, 80 mg/kg, ip) twice daily for 3 consecutive days. Mechanical paw withdrawal threshold (PWT) was used to assess pain behavior. After the rats were euthanized, spinal cords were harvested for immunoblotting analyses. The effects of minocycline on NF-κB activation were also examined in primary rat astrocytes stimulated with IL-1β in vitro. Results: BCP rats had marked bone destruction, and showed mechanical tactile allodynia on d 7 and d 14 after the operation. Intrathecal injection of minocycline (100 μg) or intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced mechanical tactile allodynia. Furthermore, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of GFAP (astrocyte marker) and PSD95 in spinal cord. Moreover, intraperitoneal injection of minocycline (80 mg/kg) reversed BCP-induced upregulation of NF-κB, p-IKKα and IκBα in spinal cord. In IL-1β-stimulated primary rat astrocytes, pretreatment with minocycline (75, 100 μmol/L) significantly inhibited the translocation of NF-κB to nucleus. Conclusion: Minocycline effectively alleviates BCP by inhibiting the NF-κB signaling pathway in spinal astrocytes.

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“…For this reason, minocycline has been widely used as a pharmacological tool to inhibit microglial cell activation, a key event involved in the central neural sensitisation induced by many noxious stimuli (Watkins and Maier 2003;Milligan and Watkins 2009). However, it has been shown that minocycline and other tetracyclines act on other cell types, such as T lymphocytes, macrophages and neurons (Amin et al 1996;Brundula et al 2002;Alano et al 2006;Kim et al 2011). Therefore, it is important to note that inhibition of peripheral macrophage activation is very likely to be an important mechanism underlying antihypernociception induced by systemic minocycline in the models in which these cells play an important role in peripheral neural sensitisation.…”

Section: Mechanisms Underlying Tetracycline Antihypernociceptive Effectsmentioning

confidence: 99%

“…Moreover, possible direct actions of tetracyclines on neuronal electrophysiological properties cannot be ruled out and thus this will be discussed (Kim et al 2011).…”

Section: Mechanisms Underlying Tetracycline Antihypernociceptive Effectsmentioning

confidence: 99%

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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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Effects of minocycline on Na+ currents in rat dorsal root ganglion neurons

Cited by 34 publications

References 57 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

Minocycline attenuates bone cancer pain in rats by inhibiting NF-κB in spinal astrocytes

Tetracyclines and pain

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