title: Limited role of macrophages in generation of nerve injury-induced mechanical allodynia.
abstract: The purpose of this study was to investigate the role of peripheral macrophages in the generation of mechanical allodynia utilizing a modification of the Chung rat model of neuropathy. Three distinct methods were used: (1) systemic and perineural macrophage inhibition utilizing CNI-1493; (2) depletion of the peripheral macrophage population by liposome-encapsulated clodronate; and (3) perineural administration of activated or inactivated bone marrow-derived macrophages (BMDM) in sham-surgery rats. Mechanical allodynia was tested on days 1, 3, 5, 7, and 10 post-intervention or surgery using von Frey monofilaments. In order to assess the role of spinal glia following these interventions, microglial (CNS macrophages) and astrocytic activation was assessed using immunohistochemistry. CNI-1493 did not attenuate mechanical allodynia, or spinal glial expression as compared to the saline control group. Similarly, the clodronate depletion of peripheral macrophages prior to nerve injury did not have any effect on the resultant mechanical allodynia or spinal glial activation. Perineural administration of activated or inactivated BMDM did not evoke mechanical allodynia in sham surgery rats. Of interest, we observed an ipsilateral, dorsal horn increase in microglial expression following perineural administration of activated macrophages. In summary, these data suggest a limited role of activated macrophages in the onset of mechanical allodynia in an animal model of neuropathy.
authors.affiliation: Department of Anesthesiology, Dartmouth-Hitchcock Medical Center, HB 7125, 1 Medical Center Drive, 03756, Lebanon, NH, USA. maria.rutkowski@dartmouth.edu
authors.forename: M D
authors.initials: MD
authors.lastname: Rutkowski
authors.forename: J L
authors.initials: JL
authors.lastname: Pahl
authors.forename: S
authors.initials: S
authors.lastname: Sweitzer
authors.forename: N
authors.initials: N
authors.lastname: van Rooijen
authors.forename: J A
authors.initials: JA
authors.lastname: DeLeo
mesh_terms: D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D016026:Bone Marrow Transplantation; D002452:Cell Count; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology; D006835:Hydrazones / Q000494:pharmacology; D006941:Hyperesthesia / Q000209:etiology* / Q000503:physiopathology; D007150:Immunohistochemistry; D008081:Liposomes; D008264:Macrophages / Q000187:drug effects / Q000502:physiology* / Q000637:transplantation; D008297:Male; D009457:Neuroglia / Q000473:pathology; D010147:Pain Measurement; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology; D013127:Spinal Nerves / Q000293:injuries*; D014950:Wounds, Penetrating / Q000150:complications* / Q000473:pathology / Q000523:psychology / Q000601:surgery; D000813:Anilides; D006146:Guanidines
chemical_list: D018712:Analgesics, Non-Narcotic; D004002:Clodronic Acid; D006835:Hydrazones; D008081:Liposomes; C097256:semapimod; D000813:Anilides; D006146:Guanidines