Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain methods
Show snapshot details
On this page
This experiment, in seven questions
Jump straight to the part of the recipe you need. Data and provenance labels stay close to the action they support.
Shopping and prep list
What do I need before I start?
Biological model pending
Subject model for the experiment.
- Use
- confirm full cohort details in the source paper
Before you run
What should be confirmed before execution?
First confirmation
Species or subject information is missing.
Confirm before execution
Protocol does not list structured equipment.
Confirm before execution
This page shows passages quoted from the paper. Equipment, materials, times, and temperatures are hidden until the page is rebuilt from the full paper and checked by a reviewer. Check the paper before using this method.
Confirm before execution
Open the source paper before finalizing run-specific details.
Procurement checkpoint
Use source-stated vendors where present. Treat mapped products as sourcing options unless the page marks an exact source match.
Open quote workflowStep-by-step procedure
What do I do, in order?
DRG macrophages are depleted by systemic AP administration
To determine whether the increase in DRG macrophages contributes to neuropathic pain development, we chose the MAFIA transgenic line, which as noted above, expresses GFP and a drug-inducible Fas suicide gene under control of the CSF1R promoter (Supplementary Fig. ). The transgene is expressed in CNS microglia (Supplementary Fig. ) and tissue macrophages, including DRG (Supplementary Fig. ). To deplete monocytic cells in the MAFIA mice, we began our studies with five daily intraperitoneal injections of AP (10 mg kg -1 ), a macrophage-depleting dose used in earlier studies. Supplementary Fig. shows that this dose was without effect on baseline mechanical threshold (S5A) and weight (S5B) in wild-type (WT) mice. By contrast, this regimen resulted in significant weight loss and also increased the baseline mechanical threshold 1 day after the last...
DRG macrophages are depleted by systemic AP administration
Using the 3-day protocol, we next used different approaches to examine the fate of resident macrophages in the DRG and of blood monocytes. We monitored DRG macrophages by immunostaining for GFP and PU.1, a transcription factor expressed in myelomonocytic cells and in their immature precursors. By the third injection, we recorded a significant loss of GFP + /PU.1 + cells (Fig. ) as well as GFP + /Iba1 + cells (Supplementary Fig. ). In a separate group of mice, 1 day after the 3-day AP regime (D3), FACS analysis demonstrated a significant, ~80% depletion of resident (GFP + ) macrophage in the L4 and L5 DRG, compared with VEH mice (Fig. ). At the same time point, FACS analysis of blood demonstrated an almost 90% depletion of mature (GFP hi or CSF1R hi ) circulating monocytes (GFP hi CD11b + or GFP + CSF1R hi ), with no change in the VEH-treated group (Supplementary Fig...
DRG macrophages are depleted by systemic AP administration
We next examined macrophages in the context of nerve injury. To monitor the early response of macrophages, we followed the expression of Cx3cr1 in the DRG by quantitative PCR (qPCR) 1 day after the nerve injury (POD1). We recorded a 2.1 ± 0.4-fold increase of Cx3cr1 expression in the L4/L5 DRG ipsilateral to the nerve injury in VEH-treated mice (Fig. ) compared with the uninjured contralateral DRG. On the other hand, AP treatment, prior to the nerve injury, not only reduced baseline Cx3cr1 expression in the uninjured, contralateral DRG but also prevented the injury-induced increase of Cx3cr1 expression in the ipsilateral DRG (Fig. ). By POD4 (5th day after the last AP treatment), macrophage number recovered to the level recorded in uninjured, VEH-treated mice (Fig. ). By POD9, the ipsilateral DRG expansion of macrophages reappeared and did not differ...
AP treatment does not alter spinal cord microglia number
Although previous studies concluded that AP does not cross the BBB, we considered it essential to rule out a direct CNS action of the AP treatment. Compared with uninjured, VEH-treated mice, we found no difference in the number of spinal cord microglia by FACS (Fig. ) in the lumbar cord of AP-treated mice. Immunostaining for microglia also did not differ (Fig. ). These results are consistent with the AP exerting a selective peripheral action. We also addressed the possibility that a compromised BBB following nerve injury could result in AP leakage into the cord,. Arguing against this possibility, both the nerve injury-induced upregulation of Cx3cr1 gene expression, evidence of microglia activation, 1 day after SNI (POD1; Fig. ) and microgliosis examined 4 days after SNI (POD4; Fig. ), did not differ between VEH- and AP-treated mice. Glial fibrillary acidic p...
DRG macrophages are required for initiation of nerve injury-induced mechanical allodynia
To investigate the contribution of DRG macrophages to nerve injury-induced mechanical hypersensitivity, we treated separate groups of mice with three daily injections of AP (1.0 mg kg -1 ) followed by SNI. In contrast to VEH-treated mice, which developed mechanical hypersensitivity within 24 h of the SNI, the 3-day AP treatment regimen significantly delayed development of the hypersensitivity, for at least 7 days after the nerve injury (Fig. ). Importantly, mice in which macrophage expansion was restored exhibited mechanical allodynia. Continuing the AP treatment into the day of nerve injury did not enhance the anti-allodynic effect (Supplementary Fig. ). These results indicate that the anti-allodynic effect of AP treatment correlates with the prevention of DRG macrophage expansion. Finally, as the AP-induced weight loss persisted in these mice (Sup...
DRG macrophages are required for initiation of nerve injury-induced mechanical allodynia
In a separate experiment we transplanted bone marrow (BM) progenitor cells (GFP + ) isolated from MAFIA mice into irradiated WT mice and confirmed the lack of effect of AP on spinal cord microglia. Specifically, 7 days after the SNI, in contrast to a complete replacement of peripheral host monocytic cells with GFP + donor cells (Supplementary Fig. ), we detected very few GFP + cells in the spinal cord (Supplementary Fig. ). We conclude that the majority of spinal cord microglia (PU1 + ) derived from the host (GFP - ), even after injury (Supplementary Fig. ). In a separate group of transplanted mice, we performed SNI after the 3-day AP or VEH treatment. Consistent with our findings in non-transplanted mice, we found that AP-mediated macrophage depletion in the DRG of the transplanted animals (Supplementary Fig. ) significantly delayed the development of ne...
Initiation of the neuropathic pain phenotype requires macrophage expansion in the DRG and is independent of infiltrat...
Next, we examined the relative contribution of macrophage expansion in the DRG and at the nerve injury site. As AP-mediated systemic macrophage depletion cannot distinguish their respective contribution, we designed the following experiment to deplete selectively macrophages at the injury site, leaving DRG macrophages intact. At the time of the nerve injury, we implanted a cannula and sutured it to muscles that overlay the injury site. Our intent was to deliver a low AP dose that only targeted the macrophages around the injury site, with limited to no systemic action. After serial dose titrations, we identified a systemic dose (0.8 µg in 20 µl) that, when administered daily for 3 days, did not influence nerve injury-induced mechanical allodynia (Supplementary Fig. ) or cause weight loss (Supplementary Fig. ). We administered the low-dose AP via the ca...
Macrophages in the DRG contribute to maintenance of nerve injury-induced mechanical allodynia
SNI-induced mechanical allodynia is typically long lasting and this behavioral phenotype is associated with prolonged microglial activation in the ipsilateral dorsal horn. Figure illustrates, e.g., that microglial activation persists for at least 4 weeks after peripheral nerve injury. At this time point, we also recorded a persistent increase in the number of macrophages in the ipsilateral DRG (Figs. a and ) and at the nerve injury site (Fig. ). Fig. 3 Microglia activation and peripheral macrophage infiltration persist at 28 days post SNI. a - c Immunostaining of Iba1 + microglia in the dorsal horn ( a ), CSF1R-GFP + macrophages (green) in the DRG ( b ), and at the nerve injury site ( c ), 28 days after SNI (POD28). NF200 (blue) labels neuronal cell bodies ( b ) and peripheral nerve myelinated axons ( c ). Dashed line in c denotes nerve ligature site. Scale bar...
Measurement outputs
What raw and processed outputs should exist?
Analysis plan
How should the outputs become interpretable results?
Acquisition
Collect raw experimental outputs with enough metadata to preserve sample identity, condition, and timing.
inferred from protocolPreprocessing / cleaning
Review raw outputs for quality, remove unusable captures, and organize the data into a comparison-ready table or image set.
inferred from protocolScoring or quantification
Quantify the primary endpoint described in the methods before moving into any statistical comparison.
inferred from protocolStatistical comparison
Statistical method not yet structured for this page.
inferred from protocolReporting output
Report representative outputs alongside the summary comparison used to support the conclusion.
inferred from protocolSource and audit
What supports the facts on this page?
Evidence quotes (8)
To determine whether the increase in DRG macrophages contributes to neuropathic pain development, we chose the MAFIA transgenic line, which as noted above, expresses GFP and a drug-inducible Fas suicide gene under control of the CSF1R promoter (Supplementary Fig. ). The transgene is expressed in CNS microglia (Supplementary Fig. ) and tissue macrophages, including DRG (Supplementary Fig. ). To deplete monocytic cells in the MAFIA mice, we began our studies with five daily intraperitoneal injections of AP (10 mg kg -1 ), a macrophage-depleting dose used in earlier studies. Supplementary Fig. shows that this dose was without effect on baseline mechanical threshold (S5A) and weight (S5B) in wild-type (WT) mice. By contrast, this regimen resulted in significant weight loss and also increased the baseline mechanical threshold 1 day after the last injection in the MAFIA mice (Supplementary Fig. ). As these effects clearly complicated our proposed analysis, we considerably tapered the dose and determined that 3 daily 1.0 mg kg -1 injections did not affect baseline mechanical (Supplementary Fig. ) or thermal (heat...
Using the 3-day protocol, we next used different approaches to examine the fate of resident macrophages in the DRG and of blood monocytes. We monitored DRG macrophages by immunostaining for GFP and PU.1, a transcription factor expressed in myelomonocytic cells and in their immature precursors. By the third injection, we recorded a significant loss of GFP + /PU.1 + cells (Fig. ) as well as GFP + /Iba1 + cells (Supplementary Fig. ). In a separate group of mice, 1 day after the 3-day AP regime (D3), FACS analysis demonstrated a significant, ~80% depletion of resident (GFP + ) macrophage in the L4 and L5 DRG, compared with VEH mice (Fig. ). At the same time point, FACS analysis of blood demonstrated an almost 90% depletion of mature (GFP hi or CSF1R hi ) circulating monocytes (GFP hi CD11b + or GFP + CSF1R hi ), with no change in the VEH-treated group (Supplementary Fig. ). Importantly, at 4 days after the last AP injection (D6 in Supplementary Fig. ), the percentage of blood monocytes was largely restored, despite a persistent weight loss (Supplementary Fig. ). Taken together, these data demonstrate that resident macrophages in the DRG, as well...
We next examined macrophages in the context of nerve injury. To monitor the early response of macrophages, we followed the expression of Cx3cr1 in the DRG by quantitative PCR (qPCR) 1 day after the nerve injury (POD1). We recorded a 2.1 ± 0.4-fold increase of Cx3cr1 expression in the L4/L5 DRG ipsilateral to the nerve injury in VEH-treated mice (Fig. ) compared with the uninjured contralateral DRG. On the other hand, AP treatment, prior to the nerve injury, not only reduced baseline Cx3cr1 expression in the uninjured, contralateral DRG but also prevented the injury-induced increase of Cx3cr1 expression in the ipsilateral DRG (Fig. ). By POD4 (5th day after the last AP treatment), macrophage number recovered to the level recorded in uninjured, VEH-treated mice (Fig. ). By POD9, the ipsilateral DRG expansion of macrophages reappeared and did not differ from that recorded in VEH-treated SNI mice (Fig. ).
Although previous studies concluded that AP does not cross the BBB, we considered it essential to rule out a direct CNS action of the AP treatment. Compared with uninjured, VEH-treated mice, we found no difference in the number of spinal cord microglia by FACS (Fig. ) in the lumbar cord of AP-treated mice. Immunostaining for microglia also did not differ (Fig. ). These results are consistent with the AP exerting a selective peripheral action. We also addressed the possibility that a compromised BBB following nerve injury could result in AP leakage into the cord,. Arguing against this possibility, both the nerve injury-induced upregulation of Cx3cr1 gene expression, evidence of microglia activation, 1 day after SNI (POD1; Fig. ) and microgliosis examined 4 days after SNI (POD4; Fig. ), did not differ between VEH- and AP-treated mice. Glial fibrillary acidic protein (GFAP) immunostaining of astrocytes also did not differ (Supplementary Fig. ). Taken together, these data confirm that neither spinal microglia nor astrocytes are affected by the AP treatment, whether or not there was a nerve injury.
To investigate the contribution of DRG macrophages to nerve injury-induced mechanical hypersensitivity, we treated separate groups of mice with three daily injections of AP (1.0 mg kg -1 ) followed by SNI. In contrast to VEH-treated mice, which developed mechanical hypersensitivity within 24 h of the SNI, the 3-day AP treatment regimen significantly delayed development of the hypersensitivity, for at least 7 days after the nerve injury (Fig. ). Importantly, mice in which macrophage expansion was restored exhibited mechanical allodynia. Continuing the AP treatment into the day of nerve injury did not enhance the anti-allodynic effect (Supplementary Fig. ). These results indicate that the anti-allodynic effect of AP treatment correlates with the prevention of DRG macrophage expansion. Finally, as the AP-induced weight loss persisted in these mice (Supplementary Fig. ), we conclude that the AP effect on mechanical hypersensitivity was not secondary to the weight loss. Moreover, because thermal pain thresholds did not differ in the AP-treated mice (Supplementary Fig. ), we conclude that systemic side effects were not major contributors...
In a separate experiment we transplanted bone marrow (BM) progenitor cells (GFP + ) isolated from MAFIA mice into irradiated WT mice and confirmed the lack of effect of AP on spinal cord microglia. Specifically, 7 days after the SNI, in contrast to a complete replacement of peripheral host monocytic cells with GFP + donor cells (Supplementary Fig. ), we detected very few GFP + cells in the spinal cord (Supplementary Fig. ). We conclude that the majority of spinal cord microglia (PU1 + ) derived from the host (GFP - ), even after injury (Supplementary Fig. ). In a separate group of transplanted mice, we performed SNI after the 3-day AP or VEH treatment. Consistent with our findings in non-transplanted mice, we found that AP-mediated macrophage depletion in the DRG of the transplanted animals (Supplementary Fig. ) significantly delayed the development of nerve injury-induced mechanical hypersensitivity (Supplementary Fig. ).
Next, we examined the relative contribution of macrophage expansion in the DRG and at the nerve injury site. As AP-mediated systemic macrophage depletion cannot distinguish their respective contribution, we designed the following experiment to deplete selectively macrophages at the injury site, leaving DRG macrophages intact. At the time of the nerve injury, we implanted a cannula and sutured it to muscles that overlay the injury site. Our intent was to deliver a low AP dose that only targeted the macrophages around the injury site, with limited to no systemic action. After serial dose titrations, we identified a systemic dose (0.8 µg in 20 µl) that, when administered daily for 3 days, did not influence nerve injury-induced mechanical allodynia (Supplementary Fig. ) or cause weight loss (Supplementary Fig. ). We administered the low-dose AP via the cannula, prior to performing the nerve injury, and repeated the targeted injection for 2 more days. By quantifying GFP + cell density 1 day after the last injection, compared with VEH-treated mice (Fig. ), we found an almost 90% reduction of macrophages (GFP + ) at the nerve injury site in the A...
SNI-induced mechanical allodynia is typically long lasting and this behavioral phenotype is associated with prolonged microglial activation in the ipsilateral dorsal horn. Figure illustrates, e.g., that microglial activation persists for at least 4 weeks after peripheral nerve injury. At this time point, we also recorded a persistent increase in the number of macrophages in the ipsilateral DRG (Figs. a and ) and at the nerve injury site (Fig. ). Fig. 3 Microglia activation and peripheral macrophage infiltration persist at 28 days post SNI. a - c Immunostaining of Iba1 + microglia in the dorsal horn ( a ), CSF1R-GFP + macrophages (green) in the DRG ( b ), and at the nerve injury site ( c ), 28 days after SNI (POD28). NF200 (blue) labels neuronal cell bodies ( b ) and peripheral nerve myelinated axons ( c ). Dashed line in c denotes nerve ligature site. Scale bar: 50 µm in a; 15 µm in b, c.
Machine-readable layer
[
{
"@context": "https://schema.org",
"@type": "HowTo",
"name": "Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain methods",
"description": "Protocol for Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain methods",
"step": [
{
"@type": "HowToStep",
"position": 1,
"name": "DRG macrophages are depleted by systemic AP administration",
"text": "To determine whether the increase in DRG macrophages contributes to neuropathic pain development, we chose the MAFIA transgenic line, which as noted above, expresses GFP and a drug-inducible Fas suicide gene under control of the CSF1R promoter (Supplementary Fig. ). The transgene is expressed in CNS microglia (Supplementary Fig. ) and tissue macrophages, including DRG (Supplementary Fig. ). To deplete monocytic cells in the MAFIA mice, we began our studies with five daily intraperitoneal injections of AP (10 mg kg -1 ), a macrophage-depleting dose used in earlier studies. Supplementary Fig. shows that this dose was without effect on baseline mechanical threshold (S5A) and weight (S5B) in wild-type (WT) mice. By contrast, this regimen resulted in significant weight loss and also increased the baseline mechanical threshold 1 day after the last..."
},
{
"@type": "HowToStep",
"position": 2,
"name": "DRG macrophages are depleted by systemic AP administration",
"text": "Using the 3-day protocol, we next used different approaches to examine the fate of resident macrophages in the DRG and of blood monocytes. We monitored DRG macrophages by immunostaining for GFP and PU.1, a transcription factor expressed in myelomonocytic cells and in their immature precursors. By the third injection, we recorded a significant loss of GFP + /PU.1 + cells (Fig. ) as well as GFP + /Iba1 + cells (Supplementary Fig. ). In a separate group of mice, 1 day after the 3-day AP regime (D3), FACS analysis demonstrated a significant, ~80% depletion of resident (GFP + ) macrophage in the L4 and L5 DRG, compared with VEH mice (Fig. ). At the same time point, FACS analysis of blood demonstrated an almost 90% depletion of mature (GFP hi or CSF1R hi ) circulating monocytes (GFP hi CD11b + or GFP + CSF1R hi ), with no change in the VEH-treated group (Supplementary Fig..."
},
{
"@type": "HowToStep",
"position": 3,
"name": "DRG macrophages are depleted by systemic AP administration",
"text": "We next examined macrophages in the context of nerve injury. To monitor the early response of macrophages, we followed the expression of Cx3cr1 in the DRG by quantitative PCR (qPCR) 1 day after the nerve injury (POD1). We recorded a 2.1 ± 0.4-fold increase of Cx3cr1 expression in the L4/L5 DRG ipsilateral to the nerve injury in VEH-treated mice (Fig. ) compared with the uninjured contralateral DRG. On the other hand, AP treatment, prior to the nerve injury, not only reduced baseline Cx3cr1 expression in the uninjured, contralateral DRG but also prevented the injury-induced increase of Cx3cr1 expression in the ipsilateral DRG (Fig. ). By POD4 (5th day after the last AP treatment), macrophage number recovered to the level recorded in uninjured, VEH-treated mice (Fig. ). By POD9, the ipsilateral DRG expansion of macrophages reappeared and did not differ..."
},
{
"@type": "HowToStep",
"position": 4,
"name": "AP treatment does not alter spinal cord microglia number",
"text": "Although previous studies concluded that AP does not cross the BBB, we considered it essential to rule out a direct CNS action of the AP treatment. Compared with uninjured, VEH-treated mice, we found no difference in the number of spinal cord microglia by FACS (Fig. ) in the lumbar cord of AP-treated mice. Immunostaining for microglia also did not differ (Fig. ). These results are consistent with the AP exerting a selective peripheral action. We also addressed the possibility that a compromised BBB following nerve injury could result in AP leakage into the cord,. Arguing against this possibility, both the nerve injury-induced upregulation of Cx3cr1 gene expression, evidence of microglia activation, 1 day after SNI (POD1; Fig. ) and microgliosis examined 4 days after SNI (POD4; Fig. ), did not differ between VEH- and AP-treated mice. Glial fibrillary acidic p..."
},
{
"@type": "HowToStep",
"position": 5,
"name": "DRG macrophages are required for initiation of nerve injury-induced mechanical allodynia",
"text": "To investigate the contribution of DRG macrophages to nerve injury-induced mechanical hypersensitivity, we treated separate groups of mice with three daily injections of AP (1.0 mg kg -1 ) followed by SNI. In contrast to VEH-treated mice, which developed mechanical hypersensitivity within 24 h of the SNI, the 3-day AP treatment regimen significantly delayed development of the hypersensitivity, for at least 7 days after the nerve injury (Fig. ). Importantly, mice in which macrophage expansion was restored exhibited mechanical allodynia. Continuing the AP treatment into the day of nerve injury did not enhance the anti-allodynic effect (Supplementary Fig. ). These results indicate that the anti-allodynic effect of AP treatment correlates with the prevention of DRG macrophage expansion. Finally, as the AP-induced weight loss persisted in these mice (Sup..."
},
{
"@type": "HowToStep",
"position": 6,
"name": "DRG macrophages are required for initiation of nerve injury-induced mechanical allodynia",
"text": "In a separate experiment we transplanted bone marrow (BM) progenitor cells (GFP + ) isolated from MAFIA mice into irradiated WT mice and confirmed the lack of effect of AP on spinal cord microglia. Specifically, 7 days after the SNI, in contrast to a complete replacement of peripheral host monocytic cells with GFP + donor cells (Supplementary Fig. ), we detected very few GFP + cells in the spinal cord (Supplementary Fig. ). We conclude that the majority of spinal cord microglia (PU1 + ) derived from the host (GFP - ), even after injury (Supplementary Fig. ). In a separate group of transplanted mice, we performed SNI after the 3-day AP or VEH treatment. Consistent with our findings in non-transplanted mice, we found that AP-mediated macrophage depletion in the DRG of the transplanted animals (Supplementary Fig. ) significantly delayed the development of ne..."
},
{
"@type": "HowToStep",
"position": 7,
"name": "Initiation of the neuropathic pain phenotype requires macrophage expansion in the DRG and is independent of infiltrat...",
"text": "Next, we examined the relative contribution of macrophage expansion in the DRG and at the nerve injury site. As AP-mediated systemic macrophage depletion cannot distinguish their respective contribution, we designed the following experiment to deplete selectively macrophages at the injury site, leaving DRG macrophages intact. At the time of the nerve injury, we implanted a cannula and sutured it to muscles that overlay the injury site. Our intent was to deliver a low AP dose that only targeted the macrophages around the injury site, with limited to no systemic action. After serial dose titrations, we identified a systemic dose (0.8 µg in 20 µl) that, when administered daily for 3 days, did not influence nerve injury-induced mechanical allodynia (Supplementary Fig. ) or cause weight loss (Supplementary Fig. ). We administered the low-dose AP via the ca..."
},
{
"@type": "HowToStep",
"position": 8,
"name": "Macrophages in the DRG contribute to maintenance of nerve injury-induced mechanical allodynia",
"text": "SNI-induced mechanical allodynia is typically long lasting and this behavioral phenotype is associated with prolonged microglial activation in the ipsilateral dorsal horn. Figure illustrates, e.g., that microglial activation persists for at least 4 weeks after peripheral nerve injury. At this time point, we also recorded a persistent increase in the number of macrophages in the ipsilateral DRG (Figs. a and ) and at the nerve injury site (Fig. ). Fig. 3 Microglia activation and peripheral macrophage infiltration persist at 28 days post SNI. a - c Immunostaining of Iba1 + microglia in the dorsal horn ( a ), CSF1R-GFP + macrophages (green) in the DRG ( b ), and at the nerve injury site ( c ), 28 days after SNI (POD28). NF200 (blue) labels neuronal cell bodies ( b ) and peripheral nerve myelinated axons ( c ). Dashed line in c denotes nerve ligature site. Scale bar..."
}
],
"tool": [],
"supply": [],
"isBasedOn": {
"@type": "ScholarlyArticle",
"headline": "Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain",
"datePublished": "2020",
"author": [
{
"@type": "Person",
"name": "Xiaobing Yu"
},
{
"@type": "Person",
"name": "Hongju Liu"
},
{
"@type": "Person",
"name": "Katherine A. Hamel"
},
{
"@type": "Person",
"name": "Maelig G. Morvan"
},
{
"@type": "Person",
"name": "Stephen Yu"
},
{
"@type": "Person",
"name": "Jacqueline Leff"
},
{
"@type": "Person",
"name": "Zhonghui Guan"
},
{
"@type": "Person",
"name": "Joao M. Braz"
},
{
"@type": "Person",
"name": "Allan I. Basbaum"
}
],
"identifier": "10.1038/s41467-019-13839-2"
}
},
{
"@context": "https://schema.org",
"@type": "BreadcrumbList",
"itemListElement": [
{
"@type": "ListItem",
"position": 1,
"name": "Experiments",
"item": "https://replicatescience.com/experiments"
},
{
"@type": "ListItem",
"position": 2,
"name": "Dorsal root ganglion macrophages contribute to both the initiation and persistence of neuropathic pain methods",
"item": "https://replicatescience.com/experiments/dorsal-root-ganglion-macrophages-contribute-to-both-the-initiation-and-persistence-of-neuropathic-pain-methods-xiaobing-yu-pmc6959328/dorsal-root-ganglion-macrophages-contribute-to-both-the-initiation-and-persistence-of-neuropathic-pa-mlpgwxxs"
}
]
}
]