Termination of Nociceptive Bahaviour at the End of Phase 2 of Formalin Test is Attributable to Endogenous Inhibitory Mechanisms, but not by Opioid Receptors Activation

Introduction: Formalin injection induces nociceptive bahaviour in phase I and II, with a quiescent phase between them. While active inhibitory mechanisms are proposed to be responsible for initiation of interphase, the exact mechanisms which lead to termination of nociceptive response in phase II are not clear yet. Phase II is a consequence of peripheral and central sensitization processes, which can lead to termination of the noxious stimuli responses 45-60 minutes after formalin injection via possible recruitment of active inhibitory mechanisms which we have investigated in this study.  Methods: To test our hypothesis, in the first set of experiments, we evaluated nociceptive response after two consecutive injection of formalin (50&muL, 2%), with intervals of 5 or 60 minutes. In the next set, formalin tests were carried out in companion with injection of Naloxone Hydrochloride, a non-selective antagonist of opioid receptors, pre-formalin injection and 30 and 45 minutes post formalin injection.  Results: While normal nociceptive behaviour was observed in the group receiving one injection of formalin, a diminished response was observed in phases I and II of those receiving consequent injection of formalin, 60 minute after first injection. While second injection of formalin, 5 minute after first injection, had no effect. Administration of naloxone (1mg/kg) decreased nociception in phase 2A but had no effect on delayed termination of formalin test.  Discussion: The results of this study suggest the existence of an active inhibitory mechanism, other than the endogenous opioids, that is responsible for termination of nociceptive behaviour at the end of formalin test

The importance of fibronectin in development, regeneration and treatment: review article

Fibronectin (FN) is one of the essential component of the extra cellular matrix and their important role is as regulator of cellular activities and also fibronectin is an important scaffold for maintaining tissue. Fibronectin conformational changes expose additional binding sites that participate in fibril formation and in conversion of fibrils into a stabilized, insoluble form. In fact fibronectin is a connected glycoprotein disulfide dimer with sedimentation coefficient of approximately S 13 and 440 kDa molecular mass which is exist in many extracellular matrix and plasma with concentration of approximately 300 µg/ml that during the regeneration body tissues acts in severely regulated stages until regenerate the damaged tissue. Fibronectin has domains for interacting with other extra cellular matrix proteins, cell surface receptors, glycosaminoglycans (GAGs), and other FN molecules. This combination of domains allows FNs to bind simultaneously to cells and to molecules within the surrounding matrix. Also fibronectin have binding sites for collagen/ gelatin, heparin, fibrinogen, and other molecules. In the present study important roles of fibronectin in development, regeneration especially in nerves system and important role of it in treatment of some diseases have been reviewed. Present study has reviewed 77 publications by using of PubMed, NCBI, Elsevier, EBSCO and Nature databases for describing the important roles of fibronectin in biological systems. Studies have shown that fibronectin has diverse roles such as: cellular adhesion, embryonic differentiation, assembly of extra cellular matrix, connecting and cell growth, transformation as well as cell migration that each of this roles depends to fibronectins action site. Considering the important role of fibronectin in attachment of cancer cells to basal lamina, spread neoplasm, tissue regeneration and formation of extra cellular matrix better identification the properties as well as physiological applications of fibronectin in tissues and bodies of animals can provide the better understanding of physiological mechanisms and pathophysiological effects of cells on each other, and also provides the new ways for treatment a variety of diseases