ABSTRACT
Traumatic brain injury (TBI) is the most prevalent health problem affecting all age groups, and leads to many secondary problems in other organs especially kidneys, gastrointestinal tract, and heart function. In this review, the search terms were TBI, fluid percussion injury, cold injury, weight drop impact acceleration injury, lateral fluid percussion, cortical impact injury, and blast injury. Studies with Actaea racemosa, Artemisia annua, Aframomum melegueta, Carthamus tinctorius, Cinnamomum zeylanicum, Crocus sativus, Cnidium monnieri, Curcuma longa, Gastrodia elata, Malva sylvestris, Da Chuanxiong Formula, Erigeron breviscapus, Panax ginseng, Salvia tomentosa, Satureja khuzistanica, Nigella sativa, Drynaria fortune, Dracaena cochinchinensis, Polygonum cuspidatum, Rosmarinus officinalis, Rheum tanguticum, Centella asiatica, and Curcuma zedoaria show a significant decrease in neuronal injury by different mechanisms such as increasing superoxide dismutase and catalase activities, suppressing nuclear factor kappa B (NF-κB), interleukin 1 (IL-1), glial fibrillary acidic protein, and IL-6 expression. The aim of this study was to evaluate the neuroprotective effects of medicinal plants in central nervous system pathologies by reviewing the available literature.
Subject(s)
Blast Injuries/prevention & control , Brain Injuries, Traumatic/prevention & control , Cold Injury/prevention & control , Gene Expression Regulation/drug effects , Neuroprotective Agents/pharmacology , Plants, Medicinal/chemistry , Animals , Blast Injuries/genetics , Blast Injuries/metabolism , Blast Injuries/pathology , Brain Injuries, Traumatic/genetics , Brain Injuries, Traumatic/metabolism , Brain Injuries, Traumatic/pathology , Catalase/genetics , Catalase/metabolism , Cerebral Cortex/drug effects , Cerebral Cortex/injuries , Cerebral Cortex/metabolism , Cold Injury/genetics , Cold Injury/metabolism , Cold Injury/pathology , Disease Models, Animal , Glial Fibrillary Acidic Protein/genetics , Glial Fibrillary Acidic Protein/metabolism , Humans , Interleukin-1/genetics , Interleukin-1/metabolism , Interleukin-6/genetics , Interleukin-6/metabolism , Mice , NF-kappa B/genetics , NF-kappa B/metabolism , Neuroprotective Agents/isolation & purification , Rats , Superoxide Dismutase/genetics , Superoxide Dismutase/metabolismABSTRACT
Nociceptive sensitization involves an increase in responsiveness of pain sensing neurons to sensory stimuli, typically through the lowering of their nociceptive threshold. Nociceptive sensitization is common following tissue damage, inflammation, and disease and serves to protect the affected area while it heals. Organisms can become sensitized to a range of noxious and innocuous stimuli, including thermal stimuli. The basic mechanisms underlying sensitization to warm or painfully hot stimuli have begun to be elucidated, however, sensitization to cold is not well understood. Here, we develop a Drosophila assay to study cold sensitization after UV-induced epidermal damage in larvae. Larvae respond to acute cold stimuli with a set of unique behaviors that include a contraction of the head and tail (CT) or a raising of the head and tail into a U-Shape (US). Under baseline, non-injured conditions larvae primarily produce a CT response to an acute cold (10°C) stimulus, however, we show that cold-evoked responses shift following tissue damage: CT responses decrease, US responses increase and some larvae exhibit a lateral body roll (BR) that is typically only observed in response to high temperature and noxious mechanical stimuli. At the cellular level, class III neurons are required for the decrease in CT, chordotonal neurons are required for the increase in US, and chordotonal and class IV neurons are required for the appearance of BR responses after UV. At the molecular level, we found that the transient receptor potential (TRP) channel brivido-1 (brv1) is required for these behavioral shifts. Our Drosophila model will allow us to precisely identify the genes and circuits involved in cold nociceptive sensitization.
Subject(s)
Calcium-Binding Proteins/physiology , Cold Injury/genetics , Dendrites/genetics , Drosophila Proteins/physiology , Hyperalgesia/genetics , Transient Receptor Potential Channels/genetics , Animals , Behavior, Animal , Cold Injury/physiopathology , Cold Temperature/adverse effects , Dendrites/metabolism , Disease Models, Animal , Drosophila melanogaster/genetics , Drosophila melanogaster/physiology , Humans , Hyperalgesia/physiopathology , Larva/genetics , Larva/physiology , Sensory Receptor Cells/metabolism , Sensory Receptor Cells/physiologyABSTRACT
BACKGROUND: Cold hyperalgesia is an intractable sensory abnormality commonly seen in peripheral neuropathies. Although glial cell line-derived neurotrophic factor family receptor alpha3 (GFRα3) is required for the formation of pathological cold pain has been revealed, potential transduction mechanism is poorly elucidated. We have previously demonstrated the contribution of enhanced activity of transient receptor potential melastatin 8 (TRPM8) to cold hyperalgesia in neuropathic pain using a rat model of chronic constriction injury (CCI) to the sciatic nerve. Recently, the enhancement of TRPM8 activity is attributed to the increased TRPM8 plasma membrane trafficking. In addition, TRPM8 can be sensitized by the activation of GFRα3, leading to increased cold responses in vivo. The aim of this study was to investigate whether GFRα3 could influence cold hyperalgesia of CCI rats via modulating TRPM8 expression and plasma membrane trafficking in dorsal root ganglion (DRG). METHODS: Mechanical allodynia, cold and heat hyperalgesia were measured on 1day before CCI and the 1st, 4th, 7th, 10th and 14th day after CCI. TRPM8 total expression and membrane trafficking as well as GFRα3 expression in DRG were detected by immunofluorescence and western blot. Furthermore, GFRα3 small interfering RNA (siRNA) was intrathecally administrated to reduce GFRα3 expression in DRG, and the effects of GFRα3 knockdown on CCI-induced behavioral sensitization as well as TRPM8 total expression and membrane trafficking in both mRNA and protein levels were investigated, and the change in coexpression of TRPM8 with GFRα3 was also evaluated. Then, the effect of GFRα3 activation with artemin on pain behavior of CCI rats pretreated with the selective TRPM8 antagonist RQ-00203078 was observed. RESULTS: Here we found that TRPM8 total expression and plasma membrane trafficking as well as GFRα3 expression in DRG were initially increased on the 4th day after CCI, and maintained at the peak level from the 10th to the 14th day, which entirely conformed with the induction and maintenance of behavioral-reflex facilitation following CCI. The coexpression of TRPM8 with GFRα3, which was mainly located in peptidergic C-fibers DRG neurons, was also increased after CCI. Downregulation of GFRα3 protein in DRG attenuated CCI-induced cold hyperalgesia without affecting mechanical allodynia and heat hyperalgesia, and reduced the upregulations of TRPM8 total expression and plasma membrane trafficking as well as coexpression of TRPM8 with GFRα3 induced by CCI. Additionally, the inhibition of TRPM8 abolished the influence of GFRα3 activation on cold hyperalgesia after CCI. CONCLUSION: Our results demonstrate that GFRα3 knockdown specially inhibits cold hyperalgesia following CCI via decreasing the expression level and plasma membrane trafficking of TRPM8 in DRG. GFRα3 and its downstream mediator, TRPM8, represent a new analgesia axis which can be further exploited in sensitized cold reflex under the condition of chronic pain.
