Nociceptive neuron

The neuropeptides are peptides acting as neurotransmitters. Some form families such as the tachykinin family with substance P, neurokinin A and neurokinin B, which consist of 11 or 12 amino acids and possess the common carboxy-terminal sequence Phe-X-Gly-Leu-Met-CONH2. Substance P is a transmitter of primary afferent nociceptive neurones. The opioid peptide family is characterized by the C-terminal sequence Tyr-Gly-Gly-Phe-X. Its numerous members are transmitters in many brain neurones. Neuropeptide Y (NPY), with 36 amino acids, is a transmitter (with noradrenaline and ATP) of postganglionic sympathetic neurones. 

Nociceptive neurons in the spinal cord as well as in higher centres such as the thalamus and cortex can also undergo alterations in activity following chronic peripheral changes and trauma (Table 1). These changes are typically long-term in nature and lead to the clinical syndromes of centrally maintained pain (secondary hyperalgesia, allodynia, spontaneous pain). Alterations... 

Oberlin E, Amara A, Bachelerie F et al (1996) The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1. Nature 382 833-835 Oh SB, Endoh T, Simen AA, Ren D, Miller RJ (2002) Regulation of calcium currents by chemok-ines and their receptors. J Neuroimmunol 123 66-75 Oh SB, Tran PB, GiUard SE, Hurley RW, Hammond DL, Miller RJ (2001) Chemokines and glycoprotein 120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci 21 5027-5035... 

Oh SB, Tran PB, GiUard SE, Hurley RW, Hammond DL, Miller RJ (2001) Chemokines and glycoprotein 120 produce pain hypersensitivity by directly exciting primary nociceptive neurons. J Neurosci 21 5027-5035... 

Budai, D., Harasawa, I., Fields, H. L. Midbrain periaqueductal gray (PAG) inhibits nociceptive inputs to sacral dorsal horn nociceptive neurons through a2-adrenergic receptors, J.Neurophysiol. 1998, 80, 2244-2254. 

Agonists at group II and group III mGlu receptors may be useful in downregulating the enhanced responses of nociceptive neurons during neuronal sensitization which involves the cAMP - PKA pathway... 

Stanfa, L. C. and Dickensen, A. H. Inflammation alters the effects of mGlu receptor agonists in spinal nociceptive neurons, Eur. J. Pharmacol. 1998, 347, 165-172. 

Qian Y, Chao DS, Santillano DR, Cornwell TL, Naim AC, Greengard P, Lincoln TM, et al. (1996) cGMP-dependent protein kinase in dorsal root gangliomrelationship with nitric oxide synthase and nociceptive neurons. J Neurosci 16 3130-8... 

Yamamura, H., Iwata, K., Tsuboi, Y., Toda, K., Kitajima, K., Shimizu, N., Nomura, H., Hibiya,J., Fujita, S., and Sumino, R. (1996). Morphological and electrophysiological properties of ACCx nociceptive neurons in rats. Brain Res. 735, 83-92. 

Ji, R. R., and Woolf, C. J. (2001). Neuronal plasticity and signal transduction in nociceptive neurons Implications for the initiation and maintenance of pathological pain. Neurobiol. Dis. 8, 1-10. 

D-Ala-deltorphin-II induces 6-opiate receptor mediated analgesia in frogs [55] and also in the invertebrate land snail (Cepaea nemoralis) [56]. When administered by intrathecal injection in rats, D-Ala-deltorphin-II produces a dose-related inhibition of the tail-flick response (threshold 0.6 nmol/rat). Its inhibitory effect lasts 10 60 min, depending on the dose, and is naltrindole reversible [57]. Wang et al. [25] demonstrated that D-Ala-deltorphin-II inhibited A6 and C fiber evoked responses from nociceptive neurons in the superficial and deeper dorsal horn of the rat medulla. 

One additional point of consideration when interpreting the above studies is to note that in pre-clinical models, retigabine and to a lesser extent ICA-27243 also affect locomotor activity. However, in general there is a separation between the MED for efficacy in pain models and the lowest dose which shows locomotor side-effects, supporting the hypothesis that Kv7 agonists are effective in pre-clinical models of pain independent of inhibiting motor function. These results in conjunction with those reported in studies on sensory neurons indicate that Kv7 activation inhibits nociceptive neuronal firing and behavioral endpoints in pre-clinical pain models. 

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