The Journal of Pain
Volume 9, Issue 6 , Pages 532-542 , June 2008

Critical Role of the Rostral Ventromedial Medulla in Early Spinal Events Leading to Chronic Constriction Injury Neuropathy in Rats

Received 5 December 2007 ,Revised 10 January 2008 ,Accepted 13 January 2008.

References 

  1. Bennett GJ, Xie Y-K. A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain. 1988;33:87–107
  2. Burgess SE, Gardell LR, Ossipov MH, Malan TP, Vanderah TW, Lai J, et al. Time-dependent descending facilitation from the rostral ventromedial medulla maintains, but does not initiate, neuropathic pain. J Neurosci. 2002;22:5129–5136
  3. Campbell JN, Meyer RA. Mechanisms of neuropathic pain. Neuron. 2006;52:77–92
  4. Carlson JD, Maire JJ, Martenson ME, Heinricher MM. Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury. J Neurosci. 2007;27:13222–13231
  5. Coull JAM, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, et al. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature. 2005;438:1017–1021
  6. Devis SM, Gonzalez-Serrin C, Betancourt M, Fernandez-Pena C, Rodriguez M, Tortorici V: Role of the endogenous pain modulatory system in the mechanism of action of gabapentin, I: Effect of the systemic administration of the anticonvulsant. Soc Neurosci Meeting, Poster No. 921.10/NN21, 2007
  7. Dougherty PM, Garrison CJ, Carlton SM. Differential influence of local anesthetic upon two models of experimentally induced peripheral mononeuropathy in the rat. Brain Res. 1992;570:109–115
  8. Fields H. State-dependent opioid control of pain. Nat Rev Neurosci. 2004;5:565–575
  9. Fields HL, Malick A, Burstein R. Dorsal horn projection targets of ON and OFF cells in the rostral ventromedial medulla. J Neurophysiol. 1995;74:1742–1759
  10. Goncalves L, Almeida A, Pertovaara A. Pronociceptive changes in response properties of rostroventromedial medullary neurons in a rat model of neuropathy. Eur J Neurosci. 2007;26:2188–2195
  11. Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain. 1988;32:77–88
  12. Heinricher MM, McGaraughty S. Analysis of excitatory amino acid transmission within the rostral ventromedial medulla: Implications for circuitry. Pain. 1998;75:247–255
  13. Heinricher MM, Morgan MM, Fields HL. Direct and indirect actions of morphine on medullary neurons that modulate nociception. Neuroscience. 1992;48:533–543
  14. Heinricher MM, Neubert MJ. Neural basis for the hyperalgesic action of cholecystokinin in the rostral ventromedial medulla. J Neurophysiol. 2004;92:1982–1989
  15. Heinricher MM, Pertovaara A, Ossipov MH. Descending modulation after injury. Prog Pain Res Manag. 2003;24:251–260
  16. Herman DS, Zhang D, Porreca F, Lai J, Vanderah TW: Spinal nerve ligation causes an increased release of cholecystokinin in the rostral ventromedial medulla. Soc Neurosci Meet Prog No. 394.16, 2005
  17. Kincaid W, Neubert MJ, Xu M, Kim CJ, Heinricher MM. Role for medullary pain facilitating neurons in secondary thermal hyperalgesia. J Neurophysiol. 2006;95:33–41
  18. Kovelowski CJ, Ossipov MH, Sun H, Lai J, Malan TP, Porreca F. Supraspinal cholecystokinin may drive tonic descending facilitation mechanisms to maintain neuropathic pain in the rat. Pain. 2000;87:265–273
  19. Laird JM, Bennett GJ. An electrophysiological study of dorsal horn neurons in the spinal cord of rats with an experimental peripheral neuropathy. J Neurophysiol. 1993;69:2072–2085
  20. Luukko M, Konttinen Y, Kemppinen P, Pertovaara A. Influence of various experimental parameters on the incidence of thermal and mechanical hyperalgesia induced by a constriction mononeuropathy of the sciatic nerve in lightly anesthetized rats. Exp Neurol. 1994;128:143–154
  21. Luukko M, Pertovaara A. Influence of an experimental peripheral mononeuropathy on the responses of medial bulboreticular neurons to noxious skin stimulation and the modulation of the responses by an α2-adrenoceptor agonist in the rat. Exp Neurol. 1993;124:390–394
  22. Millan MJ. The induction of pain: An integrative review. Prog Neurobiol. 1999;57:1–164
  23. Palecek J, Paleckova V, Dougherty PM, Carlton SM, Willis WD. Responses of spinothalamic tract cells to mechanical and thermal stimulation of skin in rats with experimental peripheral neuropathy. J Neurophysiol. 1992;67:1562–1573
  24. Paxinos G, Watson C. The Rat Brain in Stereotaxic Coordinates. 4th ed.. San Diego, CA: Academic Press; 1998;
  25. Pertovaara A. Plasticity in descending pain modulatory circuits. Prog Brain Res. 2000;129:231–242
  26. Pertovaara A, Keski-Vakkuri U, Kalmari J, Wei H, Panula P. Response properties of neurons in the rostroventromedial medulla of neuropathic rats: Attempted modulation of responses by [1DMe]NPYF, a neuropeptide FF analogue. Neuroscience. 2001;105:457–468
  27. Pertovaara A, Kontinen VK, Kalso EA. Chronic spinal nerve ligation induces changes in response characteristics of nociceptive spinal dorsal horn neurons and in their descending regulation originating in the periaqueductal gray in the rat. Exp Neurol. 1997;147:428–436
  28. Pertovaara A, Wei H, Hämäläinen MM. Lidocaine in the rostroventromedial medulla and the periaqueductal gray attenuates allodynia in neuropathic rats. Neurosci Lett. 1996;218:127–130
  29. Porreca F, Burgess SE, Gardell LR, Vanderah TW, Malan TP, Ossipov MH, et al. Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the μ-opioid receptor. J Neurosci. 2001;21:5281–5288
  30. Porreca F, Ossipov MH, Gebhart GF. Chronic pain and medullary descending facilitation. Trends Neurosci. 2002;25:319–325
  31. Sandkühler J, Benrath J, Brechtel C, Ruscheweyh R, Heinke B. Synaptic mechanisms of hyperalgesia. Prog Brain Res. 2000;129:81–100
  32. Scholz J, Broom DC, Youn D-H, Mills CD, Kohno T, Suter MR, et al. Blocking caspase activity prevents transsynaptic neuronal apoptosis and the loss of inhibition in lamina II of the dorsal horn after peripheral nerve injury. J Neurosci. 2005;25:7317–7323
  33. Sommer C. Painful neuropathies. Curr Opin Neurol. 2003;16:623–628
  34. Sotgiu ML, Biella GEM, Riva L. A study of early ongoing activity in dorsal horn units following sciatic nerve constriction. NeuroReport. 1994;5:2609–2612
  35. Sotgiu ML, Castagna A, Lacerenza M, Marchettini P. Pre-injury lidocaine treatment prevents thermal hyperalgesia and cutaneous thermal abnormalities in a rat model of peripheral neuropathy. Pain. 1995;61:3–10
  36. Suzuki R, Rahman W, Rygh LJ, Webber M, Hunt SP, Dickenson AH. Spinal-supraspinal serotonergic circuits regulating neuropathic pain and its treatment with gabapentin. Pain. 2005;117:292–303
  37. Tortorici V, Gonzalez-Serrin C, Betancourt M, Fernandez-Pena C, Devis S, Rodriguez M. Role of the endogenous pain modulatory system in the mechanism of action of gabapentin, II: Effect of the central administration of the anticonvulsant. 2007;Soc Neurosci Meeting Poster No. 921.11/NN22
  38. Tortorici V, Salas R, Nogueira L, Vanegas H. Modulation of the formalin response by on- and off-cells of the rostral ventromedial medulla. 2001;Soc Neurosci Meeting Prog. No. 161.6
  39. Tortorici V, Salas R, Vasquez D, Nogueira L, Vanegas H. Inactivation of RVM on-cells with kynurenate prevents the behavioral response to intraplantar formalin in rats. 2002;Soc Neurosci Meeting Prog No. 351.4
  40. Tortorici V, Vanegas H, Sanoja R. Simultaneous recording from spinal WDR neurons and RVM on- and off-cells upon sciatic nerve ligature that leads to chronic constriction injury: Effect of kynurenate microinjected into RVM. 2004;Soc Neurosci Meeting Prog No. 297.1
  41. Tortorici VN, Vanegas H, Sanoja R. Role of the endogenous pain modulation system in rats with peripheral neuropathy. 2003;Soc Neurosci Meeting Prog No. 481.1
  42. Trang T, Beggs S, Salter MW. Purinoceptors in microglia and neuropathic pain. Pflugers Arch Eur J Physiol. 2006;452:645–652
  43. Vanegas H. Descending control of pain during persistent peripheral damage. Rev Analg. 2007;9:55–70
  44. Vanegas H, Barbaro NM, Fields HL. Tail-flick related activity in medullispinal neurons. Brain Res. 1984;321:135–141
  45. Vanegas H, Schaible H-G. Descending control of persistent pain: Inhibitory or facilitatory?. Brain Res Rev. 2004;46:295–309
  46. Watkins LR, Meier SF. Neuropathic pain: The immune connection. Pain Clin Updates. 2004;12:1–4
  47. Wei H, Pertovaara A. MK-801, an NMDA receptor antagonist, in the rostroventral medulla attenuates development of neuropathic symptoms in the rat. NeuroReport. 1999;10:2933–2937
  48. Zhang W, Gardell SE, Xie Y, Luo M, Rance NE, Vanderah TW, et al. Pain facilitatory cells in the rostral ventromedial medulla coexpress opioid-μ receptors and cholecystokinin type 2 receptors. 2005;Soc Neurosci Prog No. 394.17
  49. Zimmermann M. Pathobiology of neuropathic pain. Eur J Pharmacol. 2001;429:23–37

 Supported in part by grant S1-2001000516 from the Venezuelan Fondo Nacional de Ciencia, Tecnologia e Innovacion (FONACIT) (to V.T.).

PII: S1526-5900(08)00370-2

doi: 10.1016/j.jpain.2008.01.332

The Journal of Pain
Volume 9, Issue 6 , Pages 532-542 , June 2008