Protective effect of alpha7 nAChR: behavioural and morphological features on neuropathy.
Traumatic, toxic or metabolic damage to the nervous system is the etiological foundation of neuropathic pain. Neuropathies are extremely difficult to treat and available drugs rarely joint an anti-hyperalgesic with a neurorestorative effect. From the literature, evidences support the alpha7 nicotinic receptor (nAChR) subtype as having a role in neuropathic pain as well as possessing neuroprotective properties. Aimed to inquire the anti-neuropathic effect of the alpha7 nAChR stimulation, we evaluated the pharmacological profile of the alpha7 nAChR agonist PNU-282987 on pain and on morphological alterations induced in the rat sciatic nerve by loose ligation (CCI). Acute administration of PNU-282987, 10 and 30 mg kg(-1) p.o. (15 days after ligation), was able to reduce hyperalgesia in a methyllicaconitine-reversed manner. This alpha7 nAChR agonist exerted no analgesic effects. Chronic PNU-282987 treatments, 30 mg kg(-1) once a day for 7 days and 10 mg kg(-1) for 28 days, were able to decrease pain perception. The histological studies highlighted that the ligation induces oedema and macrophagic infiltrate. Moreover, osmicated preparations revealed a decrease in axons' compactness and diameter, together with a significant loss of myelin sheath. Repeated treatment with PNU-282987 reduced the presence of oedema and macrophagic infiltrate and, on the coronal sections of the nerve, a significant higher myelin sheath, axonal diameter and number of fibers were observable. These results strongly suggest the pivotal role of alpha7 nAChR in the neuroprotection during neuropathy.
Pacini
Alessandra
A
University of Florence, Dept. of Preclinical and Clinical Pharmacology, Viale Pieraccini 6, 50139 Florence, Italy University of Florence, Dept. of Anatomy Histology and Forensic Medicine, Viale Morgagni 85, 50139 Florence, Italy NiKem Research S.r.l., Via Zambeletti 25, 20021 Baranzate, Milan, Italy.
Di Cesare Mannelli
Lorenzo
L
Bonaccini
Laura
L
Ronzoni
Silvano
S
Bartolini
Alessandro
A
Ghelardini
Carla
C
D000818:Animals; D001549:Benzamides / Q000627:therapeutic use*; D001643:Bridged Bicyclo Compounds / Q000627:therapeutic use*; D004195:Disease Models, Animal; D007839:Functional Laterality; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010147:Pain Measurement; D058748:Pain Perception / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000378:metabolism*; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology; D020426:Sciatic Neuropathy / Q000473:pathology / Q000517:prevention & control*; D018709:Statistics, Nonparametric; D013997:Time Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor
D001549:Benzamides; D001643:Bridged Bicyclo Compounds; C579165:Chrna7 protein, rat; D018696:Neuroprotective Agents; C498513:PNU-282987; D011978:Receptors, Nicotinic; D064569:alpha7 Nicotinic Acetylcholine Receptor