Effect of blockade of nerve growth factor and tumor necrosis factor on pain behaviors after plantar incision.
To examine the role of nerve growth factor (NGF) in postoperative pain, we administered the tyrosine kinase A (Trk A) immunoglobulin G (IgG) fusion (1 to 10 mg/kg) molecule before and after plantar incision. We also pretreated rats with a tumor necrosis factor receptor (TNFr) protein, p75 IgG fusion protein (5 to 10 mg/kg), to study the role of endogenous TNF in the development of pain behaviors after incision. Rats underwent a plantar incision, and responses to punctate and nonpunctate mechanical stimuli and withdrawal latency to radiant heat were measured. Rats were tested on the day of incision and daily for 4 days. Reduced withdrawal latency to radiant heat occurred after incision in the control group treated with IgG. Both pretreatment and treatment after incision with 5 mg/kg dose of Trk A IgG fusion protein increased the withdrawal latency to heat in incised rats (P <.05) through 4 days. A similar effect was observed after 10 mg/kg was administered after incision. Neither dose influenced the reduced withdrawal threshold and increased response to blunt mechanical stimulation caused by the incision. Pretreatment with 5 or 10 mg/kg of TNFr IgG fusion protein had no effect on any of the incision-induced pain-related behaviors. We conclude that sequestration of NGF affected responses to heat after incision but did not influence responses to mechanical stimuli. Thus, fibers sensitive to heat are influenced by NGF and probably do not contribute to exaggerated responses to mechanical stimuli. TNF does not appear to have a role in the pain behaviors.


CONCLUSIONS
To treat postoperative pain better, we should discover the factors that are causing incisional pain. One endogenous factor that contributes to pain after incision is NGF. Inhibition of NGF may provide a new way to treat pain after surgery with minimal side effects. This could improve outcome after surgery.
Zahn
Peter K
PK
Department of Anesthesia, University of Iowa, Iowa City 52242, USA.
Subieta
Alberto
A
Park
Soo Seog
SS
Brennan
Timothy J
TJ
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D018409:Foot Injuries / Q000150:complications; D006358:Hot Temperature; D007074:Immunoglobulin G / Q000494:pharmacology; D008297:Male; D020932:Nerve Growth Factor / Q000037:antagonists & inhibitors*; D010146:Pain / Q000209:etiology / Q000523:psychology*; D010812:Physical Stimulation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000037:antagonists & inhibitors*
D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D020932:Nerve Growth Factor; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases