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      General Pathways of Pain Sensation and the Major Neurotransmitters Involved in Pain Regulation

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          Abstract

          Pain has been considered as a concept of sensation that we feel as a reaction to the stimulus of our surrounding, putting us in harm’s way and acting as a form of defense mechanism that our body has permanently installed into its system. However, pain leads to a huge chunk of finances within the healthcare system with continuous rehabilitation of patients with adverse pain sensations, which might reduce not only their quality of life but also their productivity at work setting back the pace of our economy. It may not look like a huge deal but factor in pain as an issue for majority of us, it becomes an economical burden. Although pain has been researched into and understood by numerous researches, from its definition, mechanism of action to its inhibition in hopes of finding an absolute solution for victims of pain, the pathways of pain sensation, neurotransmitters involved in producing such a sensation are not comprehensively reviewed. Therefore, this review article aims to put in place a thorough understanding of major pain conditions that we experience—nociceptive, inflammatory and physiologically dysfunction, such as neuropathic pain and its modulation and feedback systems. Moreover, the complete mechanism of conduction is compiled within this article, elucidating understandings from various researches and breakthroughs.

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          Most cited references77

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          Impaired nociception and pain sensation in mice lacking the capsaicin receptor.

          The capsaicin (vanilloid) receptor VR1 is a cation channel expressed by primary sensory neurons of the "pain" pathway. Heterologously expressed VR1 can be activated by vanilloid compounds, protons, or heat (>43 degrees C), but whether this channel contributes to chemical or thermal sensitivity in vivo is not known. Here, we demonstrate that sensory neurons from mice lacking VR1 are severely deficient in their responses to each of these noxious stimuli. VR1-/- mice showed normal responses to noxious mechanical stimuli but exhibited no vanilloid-evoked pain behavior, were impaired in the detection of painful heat, and showed little thermal hypersensitivity in the setting of inflammation. Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia.
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            The glutamate receptor ion channels.

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              Nociceptors: the sensors of the pain pathway.

              Specialized peripheral sensory neurons known as nociceptors alert us to potentially damaging stimuli at the skin by detecting extremes in temperature and pressure and injury-related chemicals, and transducing these stimuli into long-ranging electrical signals that are relayed to higher brain centers. The activation of functionally distinct cutaneous nociceptor populations and the processing of information they convey provide a rich diversity of pain qualities. Current work in this field is providing researchers with a more thorough understanding of nociceptor cell biology at molecular and systems levels and insight that will allow the targeted design of novel pain therapeutics.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                MDPI
                1422-0067
                24 July 2018
                August 2018
                : 19
                : 8
                : 2164
                Affiliations
                [1 ]Department of Human Anatomy, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang 43400, Malaysia; sk.adam@ 123456upm.edu.my (S.K.A.); nizar@ 123456upm.edu.my (N.A.M.)
                [2 ]Department of Pharmacology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Malaysia; lyc14_pha052@ 123456student.usm.my (Y.C.L.); chushan@ 123456usm.my (C.S.T.)
                Author notes
                [* ]Correspondence: yammunfei@ 123456usm.my (M.F.Y.); rusliza@ 123456upm.edu.my (R.B.); Tel.: +60-465-345-86 (M.F.Y.); +60-389-472-448 (R.B.)
                Author information
                https://orcid.org/0000-0002-6274-9098
                https://orcid.org/0000-0002-9176-9661
                Article
                ijms-19-02164
                10.3390/ijms19082164
                6121522
                30042373
                0af938f7-9314-4b89-b9f7-ace785340962
                © 2018 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 19 June 2018
                : 20 July 2018
                Categories
                Review

                Molecular biology
                pain sensitization,neurotransmitters,nociceptive,inflammatory,neuropathic,presynaptic and postsynaptic,pain transmission,neurons,synaptic transmission

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