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Cholecystokinin‐8 Enhances Nerve Growth Factor Synthesis And Promotes Recovery Of Capsaicin‐Induced Sensory Deficit
Author(s) -
Manni L.,
Lundeberg T.,
Tirassa P.,
Aloe L.
Publication year - 2000
Publication title -
journal of the peripheral nervous system
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1
H-Index - 67
eISSN - 1529-8027
pISSN - 1085-9489
DOI - 10.1046/j.1529-8027.2000.absjun-3.x
Subject(s) - nerve growth factor , cholecystokinin , medicine , endocrinology , calcitonin gene related peptide , capsaicin , neuropeptide , endogeny , calcitonin , neurotrophin , peripheral , chemistry , receptor
1. Alterations of nerve growth factor (NGF) expression have been demonstrated during peripheral nerve disease and the impaired expression or synthesis and transportation of NGF has been correlated with the pathogenesis of several peripheral neuropathies. Since exogenous NGF administration seems to cause undesired side‐effects, therapeutical strategies based on the regulation of endogenous synthesis of NGF could prove useful in the clinical treatment of these disorders. 2. The aim of the present study was to analyse the effects of exogenous peripheral administration of the neuropeptide cholecystokinin‐8 (CCK‐8) on endogenous NGF synthesis, NGF mRNA and distribution of peripheral neuropeptides which are known to be regulated by this neurotrophin. 3. To address these questions we studied the effects of capsaicin (CAPS) before and after the administration of CCK‐8 on NGF levels. NGF mRNA expression and localization, and the concentration of substance P (SP) and calcitonin gene‐related peptide (CGRP) in peripheral tissue. 4. These studies demonstrate that administration of the CCK‐8 induces an increase of NGF protein and mRNA in peripheral tissue. NGF level in paw skin of CAPS/CCK‐8‐treated mice is 3 fold higher than in controls (1241 +/− 110 pg/ gr of tissue wet weight versus 414 +/− 110 pg /gr of controls) and nearly 6 fold higher than in CAPS‐treated mice (1241 +/− 110 pg/ gr versus 248 +/− 27 pg/ gr). The increase of NGF is correlated with the recovery of impaired nocifensive behaviour and with an overexpression of SP and CGRP. 5. The evidence that CCK‐8 promotes the recovery of sensory deficits suggests a potential clinical use for this neuropeptide in peripheral neuropathies.