Pain modulation

Pain sensation is modulated by glial cells communication with neuronal cells (reviewed by Scholz and Woolf 2007). The involvement of the CX3CL1/CX3CR1 pair in pain modulation has been recently demonstrated in different examples of experimental neuropathic pain induced by peripheral nerve injury or inflammation... 

Fields, H. L. Pain modulation expectation, opioid analgesia and virtual pain. Prog. Brain Res. 122 245-253, 2000. 

Norepinephrine NE transporter Human cDNA Depression, Alzheimer s disease, epilepsy, anxiety, attention deficit hyperactivity, angina, asthma, cardiac arrhythmia, cardiac hypertrophy, congestive heart failure, myocardial ischemia, hypertension, artherosclerosis, narcolepsy, orthostatic hypotension, prostatic hyperplasia, rhinitis, diabetes, diarrhea, glaucoma, impotence, obesity, opiate withdrawal pain, Raynaud s disease, preterm labor pain Modulation of norepinephrine concentration in the neuronal synaptic clefts, neuroprotection... 

Pain modulators Monoamines, acetyl choline, GABA,... 

There are various opioid receptors the three major classes of opioid receptors are mu (p), delta (5) and kappa (k) receptors. The p, receptor is the principal pain-modulating site in the CNS, mediating the action of morphine. There is considerable interest in the K receptor, which mediates a sedating analgesia with decreased addiction liability and respiratory depression and which allows for some structural flexibility. Unfortunately, the K receptor seems to be coupled to the sigma (a) receptor, which is implicated in psychotomimetic and dysphoric side effects. 

Fields FIL, Basbaum AI Central nervous system mechanisms of pain modulation. In Wall PD, Melzack R (editors) Textbook of Pain. Churchill Livingstone, 1999. 

Basbaum, A. I., Clanton, C. H., Fields, H. L. Three bulbospinal pathways from the rostral medulla of the cat an autoradiographic study of pain modulating systems, J. Comp. Neurol. 1978, 178, 209-224. 

Mason, P. Central mechanisms of pain modulation, Curr. Opin. Neurobiol. 1999, 9, 436-441. 

The role of nociceptin in pain modulation has been extensively studied, but opposite effects have been observed depending upon dose and route of administration (Barlocco et al., 2000) ... 

Langoth et al. [86] studied the properties of matrix-based tablets containing the novel pentapeptide leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) that has been shown to have pain-modulating properties. The matrix-based tablets were made with the thiolated polymer PCP. The covalent attachment of cysteine to the anionic polymer PCP leads to an improvement of the stability of matrix tablets, enhances the mucoadhesive properties, and increases the inhibitory potency of PCP towards buccal enzymes. All these factors lead to stability of the peptide and a controlled drug release for the peptide was obtained for more than 24 h. Also, the tablets based on thiolated PCP remained attached on freshly excised porcine mucosa 1.8 times longer than the corresponding unmodified polymer. 

Putative sites of action of opioid analgesics (darker color). On the left, sites of action on the pain transmission pathway from the periphery to the higher centers are shown. A Direct action of opioids on inflamed peripheral tissues. B Inhibition occurs in the spinal cord. C Possible site of action in the thalamus. Different thalamic regions project to somatosensory (SS) or limbic (L) cortex. Parabrachial nuclei (medulla/pons) projects to the amygdala. On the right, actions of opioids on pain-modulating neurons in the midbrain (D) and medulla (E) indirectly control pain transmission pathways. 

The involvement of NE in pain modulation has been demonstrated in several studies. Thus, electrical stimulation of LC or its spinal cord-projecting efferents induces an antinociceptive effect in rats (West et al., 1993 Yeomans et al., 1992). Paradoxically, lesioning of NE neurons is also increases the pain threshold (Hammond and Proudfit 1980). Other studies demonstrated as well that NE can either enhance or suppress nociception in the spinal cord and brainstem levels. It has, therefore, been suggested that different receptors mediate nociceptive and anti-nociceptive effects of NE. Pain stimulation is probably mediated via the oci-, and pain suppression via a2-adrenoceptors (Wei and Pertovaara 2006). Inflammation and sustained pain induce an increase in a2-and a decrease in oci -mediated NE transmission in the spinal cord. Thus, NE probably increases the sensitivity to acute pain and decreases it to chronic pain. 

A physiological role of Bv8-Prokineticins as peripheral and central pain modulators is supported by the observation that mice lacking the PKRs or PK2 are less sensitive to noxious stimuli than wild-type (WT) mice and exhibit impaired development of hyperalgesia after tissue injury (Hu et at, 2006 Negri et at, 2006a). 

The Delta Opioid Receptor Subtypes and Pain Modulation... 

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