Intrathecal transplantation of neuroblastoma cells decreases heat hyperalgesia and cold allodynia in a rat model of neuropathic pain.
Intrathecal grafting of cells as biological pumps to deliver monoamines, endorphins, and/or trophic factors, has been shown to be effective in treating chronic pain both in experimental animals and in clinical trials. We have tested whether intrathecal implantation of neuroblastoma cells reduces heat hyperalgesia and cold allodynia in a rat model of neuropathic pain induced by chronic constriction injury (CCI) of the sciatic nerve. Behavioral tests and cerebrospinal fluid (CSF) collection were performed before CCI, 1 week later (after which, vehicle or NB69 cells were intrathecally injected) and at 4, 7, and 14 days post-injection. Both CSF sampling and injection of the cells were performed by direct lumbar puncture. Intrathecal grafting of 4 x 10(6) NB69 neuroblastoma cells reduced to basal levels the nociceptive response to heat in nerve-injured hindpaws, while the response of control limbs remained unchanged. Similarly, the allodynic response to cold elicited by acetone evaporation decreased in the animals implanted with NB69 cells. An increase in the concentrations of dopamine and serotonin metabolites of around 150% was observed in the CSF of animals that received grafts of NB69 cells. These data suggest that the monoamines released by NB69 cells in the intrathecal space produce analgesia to neuropathic pain in rats.
De la Calle
J L
JL
Pain Unit, Hospital Ramón y Cajal, Madrid, Spain.
Mena
M A
MA
González-Escalada
J R
JR
Paíno
C L
CL
D000818:Animals; D015306:Biogenic Monoamines / Q000008:administration & dosage* / Q000134:cerebrospinal fluid; D017690:Cell Transplantation; D003080:Cold Temperature; D005260:Female; D006085:Graft Survival; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000628:therapy*; D007278:Injections, Spinal; D009447:Neuroblastoma / Q000378:metabolism* / Q000473:pathology; D010146:Pain / Q000503:physiopathology; D059408:Pain Management; D051381:Rats; D017207:Rats, Sprague-Dawley; D020426:Sciatic Neuropathy / Q000503:physiopathology / Q000628:therapy*; D014407:Tumor Cells, Cultured
D015306:Biogenic Monoamines