Effects of Fe2+ Nanoparticles on Pain Responses and Neural Oscillation Following Chronic Neuropathic Pain in Rats.

Neuropathic pain, a chronic pain condition caused by nerve damage either of the peripheral or central nervous system, responds poorly to current drug treatments. The present study aimed to investigate the analgesic and anxiolytic effect of Fe2+ nanoparticles on chronic constriction injury of sciatic nerve (CCI)-induced neuropathic pain in rats. We also assessed the effects of Fe2+ nanoparticles on brain rhythmical oscillation in rats with neuropathic pain. The CCI model was induced by four loose ligations of the left sciatic nerve. Male Wistar rats were divided into four groups: control, sham, CCI, and CCI+Fe2+ nanoparticle (1 mg/kg). The Fe2+ nanoparticle was administered by gavage on the day of CCI surgery (day 0) and daily (once a day) for 21 consecutive days after CCI surgery. Behavioral studies were conducted on days -1, 3, 7, 14, and 21 after CCI. An acetone test and elevated plus maze were performed to evaluate cold allodynia and induced anxiety-like responses, respectively. A field test was conducted to evaluate innate anxiety-like behaviors. In addition, an electrophysiological study was carried out on day 21 after CCI to assess the effects of drugs on brain wave power. Application of Fe2+ significantly reduced cold allodynia in all tested days after CCI, compared to the CCI group. The obtained data demonstrated that Fe2+ nanoparticle gavage caused analgesic and anxiolytic effects on all experimental days after CCI, compared to the CCI group. The CCI surgery significantly disturbed theta, alpha, and beta power in the brain. The application of Fe2+ nanoparticles could not significantly change brain wave power. It is suggested that Fe2+ nanoparticle has analgesic and anxiolytic effects during chronic neuropathic pain in rats. Furthermore, the CCI surgery effectively disturbed brain theta, alpha, and beta power. Nonetheless, the application of Fe2+ nanoparticles could not change deregulated brain oscillation in rats.

Saffron (Crocus sativus) ethanolic extract and its constituent, safranal, inhibits morphine-induced place preference in mice.

The effects of saffron ethanolic extract and its constituent, safranal, on the acquisition and expression of morphine-induced place preference (CPP) in male Swiss Webster mice (20-25 g) were investigated in the present study. An unbiased place conditioning method was applied for assessment of morphine reward properties. The saffron extract and safranal were administered intraperitoneally (i.p.) during (acquisition) or after induction (expression) of morphine CPP. In a pilot study, the extract and safranal were alone administered to the animals to assess if they have any reward properties. Subcutaneous (s.c.) of morphine (4 and 8 mg kg(-1)) and extract (50 mg kg(-1); i.p.) induced CPP. Extract (10, 50 and 100 mg kg(-1); i.p.) reduced the acquisition and expression of morphine CPP. The same results were obtained when safranal (1, 5 and 10 mg kg(-1), i.p.) was used. It may be concluded that both ethanolic saffron extract and safranal can inhibit the acquisition and expression of morphine-induced CPP in the mice.

Involvement of nucleus accumbens in L-arginine-induced conditioned place preference in rats.

In the present study, the effects of intraperitoneal, intra-accumbal and intra-ventral tegmental area administration of L-arginine and N(G)-nitro-L-arginine methyl-ester (L-NAME) on conditioned place preference behavior were studied. Intraperitoneal (i.p.; 0.5, 1 and 5 mg/kg) and intra-accumbal (intra-NAc; 0.3, 1 and 3 microg/rat), but not intra-ventral tegmental area (intra-VTA; 0.3, 1 and 3 microg/rat) administrations of L-arginine produced a significant place conditioning. Similar injections of L-NAME did not produce any response. However, intraperitoneal pretreatment of the animals with L-NAME (5, 10 and 20 mg/kg), 30 min before L-arginine administration, significantly abolished the acquisition of place conditioning induced by either intraperitoneal or intra-accumbal injection of L-arginine. Moreover, injection of L-NAME (5, 10 and 20 mg/kg) on the test day did not alter the L-arginine response. The results may indicate that L-arginine induces conditioned place preference via an increase in nitric oxide (NO) in the nucleus accumbens.