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We compared the inhibitory action of gabapentin, which is used to treat neuropathic pain, on mechanical allodynia induced by chemotherapeutic agents, paclitaxel, oxaliplatin, and vincristine, in mice. Single injections of paclitaxel, oxaliplatin, and vincristine at the doses corresponding to doses clinically used caused mechanical allodynia of similar intensity. Oral administration of gabapentin (30, 100 mg/kg) produced a dose-dependent inhibition of allodynia caused by paclitaxel and oxaliplatin, but not vincristine. Intrathecal injection of gabapentin (30, 100microg/site) significantly inhibited allodynia induced by paclitaxel, but not oxaliplatin and vincristine. Intraplantar injection of gabapentin (30, 100 microg/site) did not significantly inhibit allodynia induced by paclitaxel and oxaliplatin. Paclitaxel increased the expression of mRNA of voltage-dependent calcium channel alpha(2)delta-1 subunit, an action site of gabapentin, in the dorsal spinal cord, and oxaliplatin increased it in the dorsal root ganglia. Vincristine was without effects on alpha(2)delta-1 subunit mRNA in these regions. These results suggest that the efficacy of gabapentin in the treatment of mechanical allodynia is dependent on chemotherapy agent used. It may be partly due to the distinct effects of chemotherapy agents on the expression of alpha(2)delta-1 subunit of voltage-dependent calcium channel.

Abstract. This study examined in mice whether limaprost, a prostaglandin E 1 analog, would relieve allodynia induced by chemotherapeutic agents. Single intraperitoneal injections of paclitaxel, oxaliplatin, and vincristine sulfate induced and gradually increased mechanical allodynia. Repeated administration of limaprost alfadex inhibited the late, but not early, phase of mechanical allodynia induced by paclitaxel and oxaliplatin, but not vincristine. Paclitaxel and oxaliplatin, but not vincristine, gradually decreased peripheral blood flow, which was prevented by limaprost. These results suggest that limaprost is effective against mechanical allodynia induced by paclitaxel and oxaliplatin, which may be due to inhibition of the decrease in peripheral blood flow.

Introduction: Peripheral neuropathy is a common adverse effect of several anti-cancer drugs, including the platinum-based drug oxaliplatin and the taxane paclitaxel. Pain and allodynia are caused by these anti-cancer drugs, but acute dysesthesia aggravated by cold is peculiar to oxaliplatin. Objectives: In the present study, we investigated whether cold allodynia would be caused by oxaliplatin and paclitaxel and whether it would be mediated by transient receptor potential melastatin 8 (TRPM8), a cation channel activated by cold temperature and cooling agents. Methods: Male C57BL/6 mice were used. Oxaliplatin (3 mg/kg) and paclitaxel (5 mg/kg) were injected intraperitoneally. For the assessment of cold allodynia, the plantar surface was stimulated with a droplet of acetone and responses to the stimulus were ranked as follows: 0, no response; 1, lifting of the hind paw; 2, flinching or licking of the hind paw. The stimulation was applied four times and the average served as response score. The expression of TRPM8 mRNA was determined by RT-PCR methods. Results: A single injection of oxaliplatin, but not paclitaxel, caused cold allodynia which peaked on day 3 and then gradually decreased by day 25. Cold allodynia was inhibited by the TRPM8 antagonist. The expression of TRPM8 mRNA was increased in the dorsal root ganglion on day 3 after the injection of oxaliplatin, but not paclitaxel. Conclusions: Acute cold dysesthesia may be caused by oxaliplatin, but not paclitaxel, in mice. It may be at least partly due to the increased expression of TRPM8 in the primary sensory neurons. MODULATION OF NEUROPATHIC PAIN IN RATS BY THE GPR55 RECEPTORJ. Ashton, P. Brownjohn. University of Otago, Dunedin, New Zealand Introduction: GPR55 is a putative third cannabinoid G-protein coupled receptor. GPR55−/− mice show altered nociceptive thresholds compared to wildtype mice in neuropathic pain models. In addition, GPR55 is expressed in activated microglia, which are known to play a key role in modulating nociceptive transmission in the dorsal horn of the spinal cord. Objectives: We therefore aimed to determine the effects of GPR55 activation with a selective ligand on nociceptive thresholds in both healthy rats and rats with neuropathic pain. We also aimed to

Novel Coronavirus (SARS-CoV-2) first broke out in China and speeded globally. With the considerable number of Covid-19 infections and deaths, the situation has brought up major public health and governance concerns. This research study is conducted to understand if there is any association between blood group and Covid-19 disease severity. Study is conducted in Life care diagnostic and research center, New road Pokhara. A total of 1050 people who underwent RT-PCR test at Life Care Diagnostic and identified positive are used as the sample to conduct this research study. Our findings reveal that Covid-19 severity is uncommon in people with blood group O and Rh negative whereas those with blood group AB and B types are found to be severely affected. We also have an impression that individuals with rhesus negative (Rh-negative) blood groups have higher resistance for Covid-19 infection and severity.