Perineural resiniferatoxin prevents hyperalgesia in a rat model of postoperative pain.
Resiniferatoxin (RTX) is a vanilloid agonist with a unique spectrum of activities. Vanilloids bind to the transient receptor potential ion channel subtype 1, a nonselective cation ionophore important in the integration of different noxious signals. Vanilloid agonists selectively decrease sensitivity to noxious stimuli. In this study, we sought to determine whether perineural RTX prevents hyperalgesia in a model of incisional pain. In a rat model, RTX was administered percutaneously to the sciatic and saphenous nerves before the plantar incision. The withdrawal response to von Frey filaments, the struggle response to pressure on the paw, and pain scoring based on weight bearing were measured before RTX and at various intervals for 8 days after RTX. A percutaneous injection of RTX (0.0003%) to the sciatic (0.1 mL) and saphenous (0.05 mL) nerves completely prevented incisional hyperalgesia. Two hours after incision, the withdrawal threshold was 51 mN without and 456 mN with RTX (P < 0.0001). RTX also prevented the incision-induced decrease in struggle threshold and abolished the pain behavior associated with weight bearing. We conclude that RTX provides a type of neural blockade when postoperative pain is abolished and that nonpainful sensations and motor functions are preserved.
Kissin
Igor
I
*Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts; and †Department of Biostatistics, University of Alabama at Birmingham.
Davison
Natasha
N
Bradley
Edwin L
EL
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D004224:Diterpenes / Q000008:administration & dosage / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000188:drug therapy*; D008297:Male; D010149:Postoperative Pain / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000779:Anesthetics, Local; D004224:Diterpenes; C024353:resiniferatoxin
Szallasi A, Blumberg PM. Vanilloid (capsaicin) receptors and mechanisms. Pharmacol Rev 1999;51:159–212.
Caterina MJ, Julius D. The vanilloid receptor: a molecular gateway to the pain pathology. Annu Rev Neurosci 2001;24:487–517.
Petsche U, Fleischer E, Lembeck F, Handwerker HO. The effect of capsaicin application to a peripheral nerve on impulse conduction in functionally identified afferent nerve fibres. Brain Res 1983;265:233–40.
Chung JM, Lee KH, Hori Y, Willis WD. Effects of capsaicin applied to a peripheral nerve on the responses of primate spinothalamic tract cells. Brain Res 1985;329:27–38.
Pini A, Lynn B. C-fibre function during the 6 weeks following brief application of capsaicin to a cutaneous nerve in the rat. Eur J Neurosci 1990;3:274–84.
Fitzgerald M, Woolf CJ. The time course and specificity of the changes in the behavioural and dorsal horn cell responses to noxious stimuli following peripheral nerve capsaicin treatment in the rat. Neuroscience 1982;7:2051–6.
Kissin I, Bright CA, Bradley EL. Selective and long-lasting neural blockade with resiniferatoxin prevents inflammatory pain hypersensitivity. Anesth Analg 2002;94:1253–8.
Brennan TJ, Vandermeulen EP, Gebhart GF. Characterization of a rat model of incisional pain. Pain 1996;64:493–501.
Wilder RT, Sholas MG, Berde CB. NG-Nitro-l-arginine methyl ester (l-name) prevents tachyphylaxis to local anesthetics in a dose dependent manner. Anesth Analg 1996;83:1251–5.
Hahn GJ, Meeker WQ. Statistical intervals: a guide for practitioners. New York: John Wiley &Sons, 1991.
Conover WJ, Iman RL. Rank transformations as a bridge between parametric and nonparametric statistics. Am Statistician 1981;35:124–33.
Hosmer DW, Lemeshow S. Applied logistic regression. 2nd ed. New York: John Wiley &Sons, 2000:64–9.
Xu XJ, Farkas-Szallasi T, Lundberg JM, et al. Effects of the capsaicin analogue resiniferatoxin on spinal nociceptive mechanisms in the rat: behavioral, electrophysiological, and in situ hybridization studies. Brain Res 1997;752:52–60.
Wang GK, Vladimirov M, Quan C, et al. N-Butyl tetracaine as a neurolytic agent for ultralong sciatic nerve block. Anesthesiology 1996;85:1386–94.
Devor M, Schonfeld D, Seltzer Z, Wall PD. Two modes of cutaneous reinnervation following peripheral nerve injury. J Comp Neurol 1979;185:211–20.
Ainsworth A, Hall P, Wall PD, et al. Effects of capsaicin applied locally to adult peripheral nerve. II. Anatomy and enzyme and peptide chemistry of peripheral nerve and spinal cord. Pain 1981;11:379–88.
Dux M, Sann H, Schemann M, Jancso G. Changes in fibre populations of the rat hairy skin following selective chemodenervation by capsaicin. Cell Tissue Res 1999;296:471–7.
Avelino A, Cruz F. Peptide immunoreactivity and ultrastructure of rat urinary bladder nerve fibers after topical desensitization by capsaicin or resiniferatoxin. Auton Neurosci 2000;86:37–46.
Brennan TJ, Lee SK, Subieta AR, Kruger J. Behavioral effects of perineural capsaicin application in a rat model for postoperative pain. Abstracts of 10th World Congress on Pain, San Diego, CA. Seattle: IASP Press, 2002:163.
Neubert JK, Karai L, Jun JH, et al. Peripherally induced resiniferatoxin analgesia. Pain 2003;104:219–28.
Tverskoy M, Cozacov C, Ayache M, et al. Postoperative pain after inguinal herniorrhaphy with different types of anesthesia. Anesth Analg 1990;70:29–35.
Woolf CJ, Chong MS. Preemptive analgesia: treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993;77:362–79.
Kissin I. Preemptive analgesia. Anesthesiology 2000;93:1138–43.
Sinatra RS. Acute pain management and acute pain service. In: Cousins MJ, Bridenbaugh PO, eds. Neural blockade in clinical anesthesia and management of pain. 3rd ed. Philadelphia: Lippincott-Raven, 1998:815–6.
Kuzma PJ, Kline MD, Calkins MD, Staats PS. Progress in the development of ultra-long-acting local anesthetics. Reg Anesth 1997;22:543–51.