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Background & Objectives: Treatment of inflammatory pain with opioids is accompanied by unpleasant and, at times, life-threatening side effects.Cannabis produces antinociception as well as psychotropic effects. It was hypothesized that peripheral cannabinoid receptors outside the central nervous system could be selectively activated for relief of pain. This study was undertaken to measure the antinociceptive effect of type 1 cannabinoid receptor (CB1r) agonist arachidonylcyclopropylamide (ACPA) in a rat model of inflammatory pain after intrawound administration and the effects were compared with lignocaine., Methods: Wounds were produced under controlled conditions by an incision in the right hind paw in rats. ACPA (10, 30 or 100 μg/10 μl) was administered directly into the wound. Antinociception was evaluated by guarding, allodynia and thermal hyperalgesia. This was compared to lignocaine (30 μg/10 μl). Reversal of ACPA (30 μg)-mediated antinociceptive effect was attempted by intrawound AM251 (100 μg), a CB1r antagonist. Antinociception was also evaluated after contralateral administration of ACPA (30 μg). Primary afferent nociceptive input to the spinal cord was investigated by c-Fos expression after ACPA treatment (100 μg)., Results: ACPA, but not lignocaine, inhibited guarding behaviour, which was locally mediated. Conversely, lignocaine, but not ACPA, inhibited thermal hyperalgesia and mechanical allodynia. ACPA-mediated inhibitory effect was reversible and dose dependent. It was associated with a decreased c-Fos expression. Locomotor activity was unaffected following ACPA (100 μg) treatment., Interpretation & Conclusions: Lignocaine attenuated evoked pain behaviour whereas ACPA decreased guarding score. This difference was likely due to blockade of sodium ion channels and the activation of peripheral CB1r, respectively. Central side effects were absent after ACPA treatment. Further studies need to be done to assess the effect of ACPA treatment in clinical conditions.

Background & Objective: Slime is a major determinant of Staphylococcus epidermidis adherence. The established methods of laboratory detection of slime production by this organism i.e., Christensen's tube method and congo red agar plate method, can both yield inconclusive and/or intermediate results. We, therefore tried to find out electronmicroscopically the localization of slime in relation to the bacterial cell wall and look for the effect, if any of the slime location on the staphylococcal adherence as well as on the quantum of slime production., Methods: A total of 132 coagulase negative staphylococci from cases of infectious keratitis were identified as S. epidermidis following the recommended protocol. Slime was detected both by Christensen's tube method and congo red agar plate method. Antibiotic sensitivity testing was performed by standardized disc diffusion method. Adherence of the organisms to artificial surfaces was determined by a quantitative method and transmission electron microscopy was carried out by the conventional techniques., Results: Of the total 132 isolates, 57 (43.2%) were slime positive and 75 (56.8%) were slime negative. Twenty seven (47.4%) of the 57 slime producing organisms were multi drug resistant as compared to only 12 (16%) of 75 nonslime-producing organisms (P<0.001). A majority i.e., 45 (78.9%) of 57 adherent organisms were slime producers as against 12 (16%) of 75 nonadherent organisms. Electron microscopic study revealed a thick viscid layer of slime anchoring to the bacterial cell wall, especially in adherent organisms and those yielding positive slime test. Some of the organisms showed loose nonadherent slime and those were mostly nonadherent to artificial surfaces., Interpretation & Conclusion: Slime and multi drug resistance were the important virulence factors of S. epidermidis in bacterial keratitis. It was the adherent slime (i.e., slime in intimate association with the bacterial cell wall as shown by electron microscopy) only, which was responsible for resistance to multiple antibiotics and for the adhesion phenomenon observed in the quantitative slime test.

Background & Objective: The mechanism underlying the development of tolerance to morphine is not clearly understood though a number of factors have been implicated. One of the likely factors may be increased activity of anti-opioid peptides like nociceptin (also known as orphanin FQ or N/OFQ). N/OFQ and morphine bind to opioid receptor-like 1 (ORL1) receptor and muopioid receptor respectively. The present work was undertaken to investigate the density of ORL1 and mu (mu) receptor expression in the spinal cord of mice after inducing morphine tolerance., Methods: Swiss albino mice were injected with either morphine (experimental group, n=15) or saline (control, n=15), twice a day for 9 days. The development of tolerance was noted by the hotplate test. Cryostat sections of the cervical region of spinal cord were labeled with specific ligands to localize ORL1 and mu receptors. The density of receptor expression over laminae I-II of spinal cord was evaluated using image analysis system., Results: The morphine treated mice developed tolerance by day 9 as evident by the hot plate test. Both receptors were selectively expressed at a higher concentration over the superficial laminae (I-II) of the dorsal horn, indicating a role in pain processing. An increased expression of ORL1 receptors was also noted over the gray matter around the central canal. Quantitative analysis showed an increased expression of ORL1 and mu receptors though the increase was not statistically significant., Interpretation & Conclusion: The present study showed that both, ORL1 and mu-opioid receptors were expressed in areas of the spinal cord, concerned with transmission of pain signals. The density of these receptors increased in the superficial laminae (I-II) though not significantly from control after morphine tolerance. The increase in ORL1 receptors could oppose the analgesic action of morphine, contributing to tolerance. Further studies need to be done to elucidate the mechanism of morphine tolerance.