Neuropathic pain: a possible role for the melanocortin system?

Vrinten, Dorien H.; Kalkman, Cor J.; Adan, Roger A.H.; Gispen, Willem Hendrik

doi:10.1016/s0014-2999(01)01306-1

Cited by 49 publications

(38 citation statements)

References 110 publications

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“…ATF3 is a commonly used marker of DRG neuron activation, and it is also known that ATF3 regulates neurite outgrowth [22][23][24][25][26][27]. Lindwall reported that ATF3 is a c-Jun dimerization partner and that JNK-mediated c-Jun activation is associated with axonal outgrowth following axotomy of adult rat sensory neurons [25].…”

Section: Discussionmentioning

confidence: 99%

“…Seijffers demonstrated that ATF3 contributes to neurite outgrowth in injured neurons [26]. Woolf showed that the central terminals of primary afferents sprouting into lamina of the dorsal horn contribute to neuropathic pain [27]. ATF3 expression might not only represent a neural marker of injury, but may also functionally contribute to neuropathic pain.…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, after nerve injury-induced central sensitization of spinal cord neurons, large diameter, low-threshold Ab mechanoreceptors begin to sprout into lamina II of the dorsal horn and an area that normally receives only noxious information then receives input from non-noxious tactile stimuli, thus becoming capable of generating pain [26,27]. Such sprouting of Ab fibers into lamina II of the dorsal horn has been clearly observed following sciatic axotomy, partial nerve ligation and, more recently, after sciatic chronic constriction injury [28][29][30].…”

Section: Discussionmentioning

confidence: 99%

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Expression of activating transcription factor 3 (ATF3) in uninjured dorsal root ganglion neurons in a lower trunk avulsion pain model in rats

et al. 2013

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Purpose Clinically, neuropathic pain is frequent and intense following brachial plexus injury. It is thought that brachial plexus pain is not generated by avulsed roots, but rather by non-avulsed roots, since the avulsed root could not possibly transmit action potentials to central nerves. The aim of this study was to evaluate pain behavior and activation of sensory neurons in a brachial plexus avulsion (BPA) model in rats. Methods Fifteen male Wistar rats were used. In the BPA group, the C8-T1 roots were avulsed from the spinal cord with forceps at the lower trunk level (n = 5). In the naïve group, rats did not receive any procedures (n = 5). In the sham-operated group, the lower trunk was simply exposed (n = 5). Mechanical hyperalgesia of forelimbs corresponding to C6 and C7 dermatomes was measured using von Frey filaments every third day for 3 weeks. Activation of DRG neurons was immunohistochemically examined using anti-ATF3 (a marker for neuron activation) antibodies 21 days after surgery. Von Frey and immunohistochemical data between groups were analyzed using a Kruskal-Wallis test, followed by Mann-Whitney U tests. Bonferroni corrections were performed. Results Animals in the BPA group displayed significant mechanical hyperalgesia at the dermatome innervated by uninjured nerves continuing through day 21 compared with animals in the sham-operated group. ATF3-immunoreactive small and large DRG neurons were significantly activated in the BPA group (10.6 ± 9.5 and 5.2 ± 4.1 %, 39.7 ± 6.7 and 25.2 ± 10.3 %, 78.0 ± 9.1 and 53.7 ± 29.3 %) compared with the sham-operated group (0.7 ± 0.9 and 0 ± 0 %, 2.8 ± 2.0 and 1.0 ± 2.0 %, 3.9 ± 2.7 and 8.6 ± 10.1 %) at every level of C5, 6, and 7. In the naïve group, no DRG neurons were activated. ATF3-immunoreactive small and large DRG neurons were significantly activated at the level of C7 compared with C6 and C5, and significantly activated at the level of C6 compared with C5 in the BPA group. Conclusions Expression of ATF3 in uninjured DRG neurons may contribute to pain following brachial plexus avulsion injury. Consequently, spared spinal sensory nerves may represent therapeutic targets for treatment of this pain.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Expression of activating transcription factor 3 (ATF3) in uninjured dorsal root ganglion neurons in a lower trunk avulsion pain model in rats

et al. 2013

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“…11,12 Starowicz et al and other groups indicated that pain can be controlled by blockade of the MC-4 receptor because of functional interactions between the MC and opioid systems. [1][2][3][4] It also was documented that…”

Section: Introductionmentioning

confidence: 96%

“…Recent studies have shown that melanocortin (MC) receptor agonists, mainly acting via the MC-4 receptor, are involved in the modulation of nociception and function as anti-opioids, [1][2][3][4][5][6][7][8][9][10] and the MC-1 receptor also has been implicated in pain. 11,12 Starowicz et al and other groups indicated that pain can be controlled by blockade of the MC-4 receptor because of functional interactions between the MC and opioid systems.…”

Section: Introductionmentioning

confidence: 99%

Opioid and melanocortin receptors: Do they have overlapping pharmacophores?

et al. 2008

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We have identified compound 1 as a novel ligand for opioid and melanocortin (MC) receptors, which is derived from the overlapping of a well known structure for the δ opioid receptor, 2,6‐dimethyltyrosine (Dmt)‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid (Tic), and a small molecule for the MC receptor, Tic‐DPhe(p‐Cl)‐piperidin‐4‐yl‐N‐phenyl‐propionamide. Ligand 1 showed that there is an overlapping pharmacophore between opioid and MC receptors through the Tic residue. The ligand displayed high biological activities at the δ opioid receptor (Ki = 0.38 nM in binding assay, EC50 = 0.48 nM in GTP‐γ‐S binding assay, IC50 = 74 nM in MVD) as an agonist instead of an antagonist and showed selective binding affinity (IC50 = 2.3 μM) at the MC‐3 receptor rather than at the MC‐5 receptor. A study of the structure‐activity relationships demonstrated that the residues in positions 2, 3, and the C‐terminus act as a pharmacophore for the MC receptors, and the residues in positions 1 and 2 act as a pharmacophore for the opioid receptors. Thus, this structural construct can be used to prepare chimeric structures with adjacent or overlapping pharmacophores for opioid and MC receptors. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 90: 433–438, 2008.This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com

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Rational for the Use of Opioids in Nociceptive Transmission

Freye

Levy

Opioids in Medicine

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Neuropathic pain: a possible role for the melanocortin system?

Cited by 49 publications

References 110 publications

Expression of activating transcription factor 3 (ATF3) in uninjured dorsal root ganglion neurons in a lower trunk avulsion pain model in rats

Expression of activating transcription factor 3 (ATF3) in uninjured dorsal root ganglion neurons in a lower trunk avulsion pain model in rats

Opioid and melanocortin receptors: Do they have overlapping pharmacophores?

Rational for the Use of Opioids in Nociceptive Transmission

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