A thymulin analogue peptide with powerful inhibitory effects on pain of neurogenic origin.
The effects of a synthetic peptide analog of thymulin (PAT) were tested on nociceptive behavior in two animal models for peripheral mononeuropathy and in another two models for capsaicin-induced hyperalgesia. Treatment with PAT (0.25-25 microg/rat, i.p.) produced significant reduction of the mechanical allodynia and heat hyperalgesia in rats subjected to either chronic constriction injury (CCI) or spared nerve injury (SNI) models for mononeuropathy. Cold allodynia was moderately reduced in the CCI model. The inhibition of neuropathic manifestations peaked at 1-2 h post-treatment and disappeared in 3-4 h. Daily treatment with PAT, however, produced progressive attenuation of all neuropathic manifestations in the SNI model. On the other hand, pretreatment with similar doses of PAT produced dose-dependent reduction of the hyperalgesia induced by intraplantar injection of capsaicin (10 microg in 50 microl). The highest dose of PAT (50 microg) produced significant reduction of abdominal aversive behavior induced by i.p injection of capsaicin (20 microg in 100 microl). Compared with the effects of treatment with morphine or meloxicam (injected at single doses known to produce analgesia), PAT exerted equal or stronger inhibitory effects on neuropathic manifestations. The reported results suggest a possible direct action of PAT on afferent nerve fibers but its mechanisms remain to be determined.
Saadé
N E
NE
Department of Human Morphology, Faculty of Medicine, American University of Beirut, Riad El Solh, Beirut 1107-2020, Lebanon. nesaade@aub.edu.lb
Atweh
S F
SF
Jabbur
S J
SJ
Dardenne
M
M
Bach
J-F
JF
Safieth-Garabedian
B
B
D018712:Analgesics, Non-Narcotic / Q000627:therapeutic use; D000701:Analgesics, Opioid / Q000627:therapeutic use; D000818:Animals; D002211:Capsaicin / Q000009:adverse effects; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy; D008026:Ligation / Q000379:methods; D008297:Male; D000077239:Meloxicam; D009020:Morphine / Q000627:therapeutic use; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy*; D017288:Pain Threshold; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time; D013843:Thiazines / Q000627:therapeutic use; D013844:Thiazoles / Q000627:therapeutic use; D013935:Thymic Factor, Circulating / Q000031:analogs & derivatives / Q000627:therapeutic use*; D013997:Time Factors
D018712:Analgesics, Non-Narcotic; D000701:Analgesics, Opioid; D010455:Peptides; D013843:Thiazines; D013844:Thiazoles; D009020:Morphine; D013935:Thymic Factor, Circulating; D002211:Capsaicin; D000077239:Meloxicam