| Objective Neurogenic pains are caused by a primary lesion, dysfunction or transitory perturbation in the peripheral or central nervous system(CNS). Pain arising from peipheral nerve injury is one of the most disabling and refractory disabilities known to exist. Allodynia (nociceptive reaction to innocuous stimuli) and hyperalgesia(increased reactivity to nociceptive stimuli)considered as the main neuropathic manifestations. Various clinical strategies have been designed to deal with the different pathophysiological mechanisms underlying neuropathic pain, including sympatholytics, tidepressants, antiepileptics and various anti-inflammatory drugs or their various combinations. Depending on the dosage, the method of administration and the etiology of neuropathic manifestations, each class of substances elicited preferential effects either on allodynia or hyperalgesia, which were often accompanied by moderate or important side effect. The diversity of neuropathic pains and the difficulties encountered in their treatments have lead to the search for the development of animal models simulating these pains and the screening of the potential analgesic effects with classical or newly designed drugs. Lactoferrin(LF) is a single-chain glycoprotein with a molecular weight of about 80,000 that belongs to the family of transferrins. It is found in milk, neutrophils, and other biological fluids, and has many peripheral functions, inducing primary defense against microbial infection, immunomodulation, and cell growth regulation. More recently, a role for BLF reduces nociception in various acute pain models, as formalin test, hot plate test, and acetic acid writhing test in rats has been described. On the other hand, the tuber of the species Aconitum is a crude drug that had been utilized since ancient times. The well-known analgesic effect of processed Aconiti tuber(PAT) is derived from the pharmacological actions of the aconitine alkaloids, including aconitine mesaconitine,and benzoylmesaconitine. The anti-nocicetptive effect of PAT has been demonstrated in animal models of acute nociceptive pain. To date,however,the analgesic effects of LF and PAT on neuropathic pain have not been evaluated. The aims of this study were firstly to investigate the possible analgesic effects of BLF on neurgenic pains. These effects have screened on the CCI and SNI animal model for neuropathic pain. Secondly to investigate the possible analgesic effects of processe Aconiti tuber on neurgenic pains and thirdly to test whether co-administration of LF could potent antinociceptive activity of processe Aconiti tuber. Method This study was conducted in four parts. 1. 152 male SD rats weighing 180-250g were randomly divided into nineteen groups(n=8). 14 days after CCI surgery (partial ligation of the right sciatic nerve), in groups 1~6,rats received intrathecal (IT) administration of durgs:IT saline in 10μl; IT lactoferrin 10, 100 or 1000μg/kg in 10μl of normal saline; IT lactoferrin100μg + IT Nalxone100μg; IT lactoferrin100μg + IT nor-binaltorphimine(norBNI)100μg; in groups 7~13,rats received intraperitoneal(IP) administration of durgs: IP saline 1ml; IP lactoferrin 0.5, 1 or 2g/kg in 1ml NS; IP lactoferrin(2g/kg)+ IP Nalxone (1mg/kg); IP lactoferrin(2g/kg)+ IP Nalxone (2mg/kg); IP Nalxone (2mg/kg);in groups 14~16,rats received oral administration of durgs:a single oral dose of saline in 1ml or lactoferrin 2, 4 g/kg in 1ml of NS. In groups 17~19, rats received multi-day oral doses of saline 1ml or lactoferrin 1, 2g/kg·day in 1ml for 14 days after surgery. 2. 40 male SD rats weighing 110-130g were randomly divided into 5 groups(n=8). 5 days after SNI surgery(ligation of L5,L6), rats received IP saline in 1ml, IP lactoferrin 0.5, 1, 2g/kg in 1ml NS, IP lactoferrin(2g/kg)+ IP Nalxone (2mg/kg).3. 64 male SD rats weighing 180-250g were randomly divided into eight groups (n=8). 14 days after CCI surgery rats received oral administration of saline 1ml, PAT 0.5,1,2, 4g/kg, oral PAT 2g/kg +IP Nalxone 2mg/kg , oral PAT 2g/kg +IP norBNI 2mg/kg,oral PAT 2g/kg + IT norBNI 100μg. 4. 104 male SD rats weighing 180-250g were randomly divided into thirteen groups(n=8). 14 days after CCI surgery, rats received oral saline 1ml or PAT 0.5, 1, 2, 4g/kg; IP saline 1ml or BLF 0.5, 1, 2g/kg; or oral saline 1ml, or oral PAT 0.5, 1, 2g/kg combined with the lowest dose (0.5g/kg) of IP BLF. As indicators of mechanical and heat hyperalgesia, the pressure threshold of the paw withdrawal in response to a graded pressure stimulus with a filament and the paw withdrawal latency in response to radiant heat were measured on both hind paws before and after drugs administration. Result 1.After CCI and by the time of drug tests, both pressure threshold and latency decreased significantly only in the right paw. IT and IP. BLF significantly increased pressure threshold and latency. These effects of BLF were completely inhibited by naloxon, a μ-opioid receptor antagonist. but not by nor-binaltorphimine, a κ-opioid receptor antagonist. Single or multiple oral doses of BLF did not affect pressure threshold or latency. 2. After SNI and by the time of drug tests, both von Frey and latency decreased significantly only in the right paw. IP BLF significantly increased pressure threshold and latency. These effects of BLF were completely inhibited by naloxon. 3. After CCI and by the time of drug tests,both pressure threshold and latency had decreased significantly only in the right paw. Oral PAT increased pressure threshold and latency. The increase in pressure threshold and latency were much greater in the right paw than in the left paw. The effects of oral PAT were completely inhibited by IP as well as IT nor-BNI,a κ-opioid receptor antagonist. 4. After CCI and by the time of drug tests, both pressure threshold and latency decreased significantly only in the right paw. PAT alone increased the... |
PDF Full Text Request