Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain

Tutkimustuotos: ArtikkelijulkaisuArtikkeliTieteellinenvertaisarvioitu

Kuvaus

Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII+ spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα)+ microglia/macrophages were found in the PFC of SNI rats. Interestingly in naïve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII+/CD172a+ ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII+ microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain.
Alkuperäiskielienglanti
LehtiBrain, Behavior, and Immunity
Vuosikerta58
NumeroNovember
Sivut107-117
Sivumäärä11
ISSN0889-1591
DOI - pysyväislinkit
TilaJulkaistu - 1 kesäkuuta 2016
OKM-julkaisutyyppiA1 Alkuperäisartikkeli tieteellisessä aikakauslehdessä, vertaisarvioitu

Tieteenalat

  • 3112 Neurotieteet

Lainaa tätä

@article{8260acc7c45043e8be3207532242541a,
title = "Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain",
abstract = "Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII+ spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα)+ microglia/macrophages were found in the PFC of SNI rats. Interestingly in na{\"i}ve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII+/CD172a+ ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII+ microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain.",
keywords = "3112 Neurosciences",
author = "Zhilin Li and Hong Wei and Piirainen, {Sami Lauri Juhani} and Zuyue Chen and Kalso, {Eija Anneli} and Pertovaara, {Antti Yrj{\"o}} and Li Tian",
year = "2016",
month = "6",
day = "1",
doi = "10.1016/j.bbi.2016.05.021",
language = "English",
volume = "58",
pages = "107--117",
journal = "Brain, Behavior, and Immunity",
issn = "0889-1591",
publisher = "ACADEMIC PRESS INC ELSEVIER SCIENCE",
number = "November",

}

TY - JOUR

T1 - Spinal versus brain microglial and macrophage activation traits determine the differential neuroinflammatory responses and analgesic effect of minocycline in chronic neuropathic pain

AU - Li, Zhilin

AU - Wei, Hong

AU - Piirainen, Sami Lauri Juhani

AU - Chen, Zuyue

AU - Kalso, Eija Anneli

AU - Pertovaara, Antti Yrjö

AU - Tian, Li

PY - 2016/6/1

Y1 - 2016/6/1

N2 - Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII+ spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα)+ microglia/macrophages were found in the PFC of SNI rats. Interestingly in naïve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII+/CD172a+ ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII+ microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain.

AB - Substantial evidence indicates involvement of microglia/macrophages in chronic neuropathic pain. However, the temporal-spatial features of microglial/macrophage activation and their pain-bound roles remain elusive. Here, we evaluated microglia/macrophages and the subtypes in the lumbar spinal cord (SC) and prefrontal cortex (PFC), and analgesic-anxiolytic effect of minocycline at different stages following spared nerve injury (SNI) in rats. While SNI enhanced the number of spinal microglia/macrophages since post-operative day (POD)3, pro-inflammatory MHCII+ spinal microglia/macrophages were unexpectedly less abundant in SNI rats than shams on POD21. By contrast, less abundant anti-inflammatory CD172a (SIRPα)+ microglia/macrophages were found in the PFC of SNI rats. Interestingly in naïve rats, microglial/macrophage expression of CD11b/c, MHCII and MHCII+/CD172a+ ratio were higher in the SC than the cortex. Consistently, multiple immune genes involved in anti-inflammation, phagocytosis, complement activation and M2 microglial/macrophage polarization were upregulated in the spinal dorsal horn and dorsal root ganglia but downregulated in the PFC of SNI rats. Furthermore, daily intrathecal minocycline treatment starting from POD0 for two weeks alleviated mechanical allodynia most robustly before POD3 and attenuated anxiety on POD9. Although minocycline dampened spinal MHCII+ microglia/macrophages until POD13, it failed to do so on cortical microglia/macrophages, indicating that dampening only spinal inflammation may not be enough to alleviate centralized pain at chronic stage. Taken together, our data provide the first evidence that basal microglial/macrophage traits underlie differential region-specific responses to SNI and minocycline treatment, and suggest that drug treatment efficiently targeting not only spinal but also brain inflammation may be more effective in treating chronic neuropathic pain.

KW - 3112 Neurosciences

U2 - 10.1016/j.bbi.2016.05.021

DO - 10.1016/j.bbi.2016.05.021

M3 - Article

VL - 58

SP - 107

EP - 117

JO - Brain, Behavior, and Immunity

JF - Brain, Behavior, and Immunity

SN - 0889-1591

IS - November

ER -