Adoptive transfer of peripheral immune cells potentiates allodynia in a graded chronic constriction injury model of neuropathic pain.
Recent evidence demonstrates that peripheral immune cells contribute to the nociceptive hypersensitivity associated with neuropathic pain by infiltrating the central nervous system (CNS). We have recently developed a rat model of graded chronic constriction injury (CCI) by varying the exposure of the sciatic nerve and control non-nerve tissue to surgical placement of chromic gut. We demonstrate that splenocytes can contribute significantly to CCI-induced allodynia, as adoptive transfer of these cells from high pain donors to low pain recipients potentiates allodynia (P<0.001). The phenomenon was replicated with peripheral blood mononuclear cells (P<0.001). Adoptive transfer of allodynia was not achieved in sham recipients, indicating that peripheral immune cells are only capable of potentiating existing allodynia, rather than establishing allodynia. As adoptively transferred cells were found by flow cytometry to migrate to the spleen (P<0.05) and potentiation of allodynia was prevented in splenectomised low pain recipients, adoptive transfer of high pain splenocytes may induce the migration of host-derived immune cells from the spleen to the CNS as observed by flow cytometry (P<0.05). Importantly, intrathecal transfer of CD45(+) cells prepared from spinal cords of high pain donors into low pain recipients led to potentiated allodynia (P<0.001), confirming that infiltrating immune cells are not passive bystanders, but actively contribute to nociceptive hypersensitivity in the lumbar spinal cord.
Discipline of Pharmacology, School of Medical Sciences, University of Adelaide, Adelaide 5005, Australia. peter.grace@adelaide.edu.au
Peter M
PM
Grace
Mark R
MR
Hutchinson
Alan
A
Bishop
Andrew A
AA
Somogyi
Graham
G
Mayrhofer
Paul E
PE
Rolan
D019264:Adoptive Transfer; D000704:Analysis of Variance; D000818:Animals; D005434:Flow Cytometry; D006930:Hyperalgesia / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000637:transplantation*; D008297:Male; D009437:Neuralgia / Q000276:immunology*; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000276:immunology / Q000293:injuries*; D013156:Splenectomy