A Minimal CGRP Gene Promoter is Inducible by Nerve Growth Factor in Adult Rat Dorsal Root Ganglion Neurons But Not in PC12 Phaeochromocytoma Cells

Watson, Andrea; Ensor, Elizabeth; Symes, Aviva J.; Winter, Janet; Kendall, G M; Latchman, David S.

doi:10.1111/j.1460-9568.1995.tb00335.x

Cited by 31 publications

(18 citation statements)

References 41 publications

(61 reference statements)

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“…Neurotrophins can also influence the cellular expression of neuropeptides such as CGRP, SP, and NPY (e.g., Goedert et al, 1981;Schwartz et al, 1982;Fitzgerald et al, 1985;Lindsay and Harmar, 1989;Wong and Oblinger, 1991 Jones et al, 1994;Mulderry, 1994;Verge et al, 1995;Watson, 1995). It can therefore not be excluded that the changed expression of neuropeptides during aging, or as a result of axotomy, is mediated by changes in the availability of neurotrophins and/or the expression of the neurotrophin receptors.…”

Section: Discussionmentioning

confidence: 95%

“…With regard to sensory neurons, it has been demonstrated that axonal injury also influences expression of neurotrophin receptors (Verge et al, 1989(Verge et al, , 1992. Moreover, several studies have shown that the expression of a number of neuropeptides such as CGRP, SP, and NPY in sensory neurons can be influenced by neurotrophic factors (e.g., Goedert et al, 1981;Schwartz et al, 1982;Fitzgerald et al, 1985;Lindsay and Harmar, 1989;Wong and Oblinger, 1991;Jones et al, 1994;Mulderry, 1994;Verge et al, 1995;Watson, 1995). Based on these evidences, it has been suggested that the changes in neuropeptide expression seen in sensory neurons following axonal lesions may at least in part be the result of decreased neurotrophic signalling.…”

mentioning

confidence: 96%

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Neuropeptides and neurotrophin receptor mRNAs primary sensory neurons of aged rats

Bergman

Johnson

et al. 1996

J. Comp. Neurol.

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Neuropeptides and neurotrophin receptors are regulated in primary sensory neurons in response to axonal injury, and axonal lesions are characteristic stigmata of aging primary sensory neurons. We have therefore examined the expression of neuropeptides and neurotrophin receptor mRNAs in 30-month-old (median survival age) Sprague-Dawley rats to see if similar adaptive mechanisms operate in senescence. The content of neuropeptides was examined with immunohistochemistry (IHC) and in situ hybridization (ISH), and the cellular mRNA expression of neurotrophin receptors was studied with ISH. All of the aged rats had symptoms of hind limb incapacity (posterior paralysis), but fore limbs did not seem affected. The size-distribution of neuronal profiles in cervical and lumbar dorsal root ganglia (DRGs) was similar in aged and young adult (2-3 months old) rats. In aged rats, the DRG neurons showed an increase in both immunolabelling and mRNA content of neuropeptide tyrosine (NPY), as well as an increased cellular expression of galanin mRNA. In the same animals, there were decreased cellular levels of calcitonin gene-related peptide (CGRP; IHC and ISH) and substance P (SP; IHC and ISH), while the difference in neuronal somatostatin (IHC and ISH) was small. The distribution of neuropeptide immunoreactivities in the dorsal horn of the corresponding spinal cord segments revealed a decreased labelling for CGRP-, SP-, and somatostatin-like immunoreactivities (LI) in the aged rats at both cervical and lumbar levels. NPY- and galanin-LI had a similar distribution in aged and young adult rats. NPY-immunoreactive fibers were also encountered in the dorsal column of aged but not young adult rats. ISH revealed that most of the primary sensory neurons express mRNA for the p75 low-affinity neurotrophin receptor (p75-LANR) and that there was no discernible difference between young adult and aged rats. The labelling intensity for mRNA encoding high-affinity tyrosine kinase receptors (TrkA, TrkB, and TrkC) was decreased in aged rat DRG neurons, while the percentage of neuronal profiles expressing mRNA for TrkA/B/C was similar in young adult and aged rats. The changed pattern of neuropeptide expression in primary sensory neurons of aged rats resembled that seen in young adult rats subjected to axonal injury of peripheral sensory nerves and may, thus, indicate aging-related lesions of sensory fibers. Since NPY is primarily present in large and galanin in small DRG neurons, the stronger effect on NPY as compared to galanin expression may indicate that aging preferentially affects neurons associated with mechanoreception (A alpha and A beta fibers) as compared to nociceptive units (A delta and C fibers). Furthermore, the observed changes in neuropeptide expression were most pronounced in lumbar DRGs, that harbors the sensory neurons supplying the affected hindlimbs of the rats.

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Section: Discussionmentioning

confidence: 95%

mentioning

confidence: 96%

Neuropeptides and neurotrophin receptor mRNAs primary sensory neurons of aged rats

Bergman

Johnson

et al. 1996

J. Comp. Neurol.

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“…In the mature nervous system, neurotrophins have been implicated to be important in the balance between growth and retraction of terminal nerve fibers (Purves, 1988;Cowen, 1993), in axonal regeneration after injury (Heumann et al, 1987;Meyer et al, 1992;Funakoshi et al, 1993), and in regulating neuropeptide expression (Goedert et al, 1981;Fitzgerald et al, 1985;Lindsay and Harmar, 1989;Mulderry, 1994;Watson et al, 1995;Verge et al, 1995), as well as neurofilament expression (Gold et al, 1991;Parhad et al, 1995). All of these functions are highly relevant in the complex process of aging (see also introductory remarks).…”

Section: Trk Expression Declines In Aged Primary Sensory Neuronsmentioning

confidence: 97%

Effects of aging and axotomy on the expression of neurotrophin receptors in primary sensory neurons

1999

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“…Furthermore, the MEK1 (mitogenactivated protein kinase/extracellular signal-regulated kinase kinase) inhibitor, PD98059, which blocks the MAPK pathway, inhibited morphine-induced increased expression of CGRP-LI and SP-LI, as well as phosphorylation of ERK and CREB in cultured DRG neurons [70] . Other studies have shown that ERK/MAPK activated CREB in various cell types in vitro [74] and in different brain regions in vivo [75] , and that both CGRP and preprotachykinin gene promoters contain CRE [76][77][78][79] . Thus, chronic morphine exposure appears to enhance the expression of nociceptive sensory neuropeptides such as CGRP and SP via ERK/MAPK pathway and is CREB dependent.…”

Section: Protein Kinase Activationmentioning

confidence: 99%

Is Paradoxical Pain Induced by Sustained Opioid Exposure an Underlying Mechanism of Opioid Antinociceptive Tolerance?

et al. 2005

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Opiates are the primary treatment for pain management in cancer patients reporting moderate to severe pain, and are being increasingly used for non-cancer chronic pain. However, prolonged administration of opiates is associated with significant problems including the development of antinociceptive tolerance, wherein higher doses of the drug are required over time to elicit the same amount of analgesia. High doses of opiates result in serious side effects such as constipation, nausea, vomiting, dizziness, somnolence, and impairment of mental alertness. In addition, sustained exposure to morphine has been shown to result in paradoxical pain in regions unaffected by the initial pain complaint, and which may also result in dose escalation, i.e. ‘analgesic tolerance’. A concept that has been gaining considerable experimental validation is that prolonged use of opioids elicits paradoxical, abnormal pain. This enhanced pain state requires additional opioids to maintain a constant level of antinociception, and consequently may be interpreted as antinociceptive tolerance. Many substances have been shown to block or reverse antinociceptive tolerance. A non-inclusive list of examples of substances reported to block or reverse opioid antinociceptive tolerance include: substance P receptor (NK-1) antagonists, calcitonin gene-related peptide (CGRP) receptor antagonists, nitric oxide (NO) synthase inhibitors, calcium channel blockers, cyclooxygenase (COX) inhibitors, protein kinase C inhibitors, competitive and non-competitive antagonists of the NMDA (N-methyl-D-aspartate) receptor, AMPA (alpha-amino-3-hydroxy-5-methyl-4 isoxazolepropionic acid) antagonists, anti-dynorphin antiserum, and cholecystokinin (CCK) receptor antagonists. Without exception, these substances are also antagonists of pain-enhancing agents. Prolonged opiate administration indeed induces upregulation of substance P (SP) and calcitonin gene-related peptide (CGRP) within sensory fibers in vivo, and this is accompanied by an enhanced release of excitatory neurotransmitters and neuropeptides from primary afferent fibers upon stimulation. The enhanced evoked release of neuropeptides is correlated with the onset of abnormal pain states and opioid antinociceptive tolerance. Importantly, the descending pain modulatory pathway from the brainstem rostral ventromedial medulla (RVM) via the dorsolateral funiculus (DLF) is critical for maintaining the changes observed in the spinal cord, abnormal pain states and antinociceptive tolerance, because animals with lesion of the DLF did not show enhanced evoked neuropeptide release, or develop abnormal pain or antinociceptive tolerance upon sustained exposure to opiates. Microinjection of either lidocaine or a CCK antagonist into the RVM blocked both thermal and touch hypersensitivity as well as antinociceptive tolerance. Thus, prolonged opioid exposure enhances a descending pain facilitatory pathway from the RVM that is mediated at least in part by CCK activity and is essential for the maintenance of antinociceptive tolerance.

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A Minimal CGRP Gene Promoter is Inducible by Nerve Growth Factor in Adult Rat Dorsal Root Ganglion Neurons But Not in PC12 Phaeochromocytoma Cells

Cited by 31 publications

References 41 publications

Neuropeptides and neurotrophin receptor mRNAs primary sensory neurons of aged rats

Neuropeptides and neurotrophin receptor mRNAs primary sensory neurons of aged rats

Effects of aging and axotomy on the expression of neurotrophin receptors in primary sensory neurons

Is Paradoxical Pain Induced by Sustained Opioid Exposure an Underlying Mechanism of Opioid Antinociceptive Tolerance?

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