ABSTRACT
Prokineticin 2 (PK2) is a newly discovered chemokine, which participates in various physiological functions of the body by binding to receptors PKR1 and PKR2. PK signaling pathway is a newly discovered important regulatory pathway for the occurrence and maintenance of pain after tissue injury and nerve injury in recent years. It plays a key role in regulating injury-related nociceptive events and is a potential therapeutic target for many diseases. The activation of PKRs can induce pain sensation and participate in the sensitivity of pain receptors to different stimuli. The PK system (PKs and PKRs) is an important link involved in inflammation and pain transmission in immune cells. PK2 is involved in the regulation of pain perception by activating PKR1 and PKR2 on primary sensory neurons. In rat primary sensory neurons, PK2 also enhances gated ion channel current through the PKC signaling pathway, inhibits GABA-activated currents, and sensitizes purine nucleotide P2 receptor (P2X). This paper reviews the research progress of PK2 in physical pain. We hope to find new drugs for the treatment of inflammatory pain that target the PKs signaling pathway in future studies.
ABSTRACT
Tweety-homolog 1 (Ttyh1) is expressed in neural tissue and has been implicated in the generation of several brain diseases. However, its functional significance in pain processing is not understood. By disrupting the gene encoding Ttyh1, we found a loss of Ttyh1 in nociceptors and their central terminals in Ttyh1-deficient mice, along with a reduction in nociceptor excitability and synaptic transmission at identified synapses between nociceptors and spinal neurons projecting to the periaqueductal grey (PAG) in the basal state. More importantly, the peripheral inflammation-evoked nociceptor hyperexcitability and spinal synaptic potentiation recorded in spinal-PAG projection neurons were compromised in Ttyh1-deficient mice. Analysis of the paired-pulse ratio and miniature excitatory postsynaptic currents indicated a role of presynaptic Ttyh1 from spinal nociceptor terminals in the regulation of neurotransmitter release. Interfering with Ttyh1 specifically in nociceptors produces a comparable pain relief. Thus, in this study we demonstrated that Ttyh1 is a critical determinant of acute nociception and pain sensitization caused by peripheral inflammation.
ABSTRACT
Good pain control after surgery is important to facilitate overall recovery, improve patient satisfaction, decrease morbidity, and reduce health care cost. However, despite heightened awareness and development of new guidelines in recent decades, we have failed to make major improvements in postoperative pain control. Currently available analgesic therapies have limited efficacy, and pain after surgery continues to be a significant clinical problem. Our goal is to develop more effective and safer clinical strategies that will eliminate or greatly reduce postoperative pain, and a better understanding of the mechanisms of pain induced by surgery would be essential to achieve this goal. Evidence suggests that the pathophysiological mechanisms and optimal treatment of postoperative pain are different from many other painful conditions. Recognizing the necessity and importance of relevant pre-clinical models, we have developed and characterized rodent incision models that have close similarities to postoperative pain in patients. Previous studies have demonstrated the clinical relevance and translatability of these pre-clinical models of postoperative pain. In this review, we describe the rodent incision pain models, and summarized our current understanding of the mechanisms of postoperative pain, highlighting key findings from our previous studies using these models.
Subject(s)
Humans , Central Nervous System Sensitization , Health Care Costs , Pain, Postoperative , Patient Satisfaction , RodentiaABSTRACT
ABSTRACT BACKGROUND AND OBJECTIVES: Trigeminal neuralgia is one of the most common neuropathic pains that compromise head and neck. It manifests as shock or burning pain normally evoked by non-noxious facial stimulations. Its etiopathology is not totally understood, but it is known that different mechanisms contribute to the establishment and maintenance of pain. This study aimed to address current contexts of epidemiology, diagnosis, management and pathophysiological mechanisms underlying trigeminal neuralgia in peripheral and central nervous systems. CONTENTS: Inflammation and release of inflammatory mediators, neuropeptides and neurotrophic factors, as well as degenerative changes of nervous fibers caused by direct nervous injury are relevant peripheral mechanisms which lead to altered sensitivity of nociceptive neurons, development of spontaneous and exacerbated activity, allodynia and hyperalgesia. Among central mechanisms, exacerbated activation of central nociceptive neurons, neuroplasticity, changes in electrophysiological properties and neuronal hyperexcitability, in addition to changes in modulatory pain controls, lead to pain establishment and maintenance. CONCLUSION: Several mechanisms are involved in neuropathic pains, both in peripheral and central levels, although specific trigeminal neuralgia events are not totally described. Studies concerning its specific neurobiology are needed to understand functional and behavioral changes, which can contribute to trigeminal neuralgia clinical management and treatment.
RESUMO JUSTIFICATIVA E OBJETIVOS: A neuralgia do trigêmeo é uma das dores neuropáticas mais comumente encontradas na região de cabeça e pescoço e manifesta-se como crises de choque ou queimação geralmente desencadeadas por estímulos não dolorosos na região da face. A sua etiopatogenia não é totalmente conhecida, mas sabe-se que diversos mecanismos contribuem para seu estabelecimento. O objetivo deste estudo foi abordar os contextos atuais de epidemiologia, diagnóstico, tratamento e mecanismos fisiopatológicos subjacentes à neuralgia do trigêmeo nos sistemas nervoso periférico e central. CONTEÚDO: A inflamação e a liberação de mediadores inflamatórios, neuropeptídeos e fatores neurotróficos, assim como alterações degenerativas das fibras nervosas decorrentes da lesão nervosa direta são mecanismos periféricos relevantes que, em conjunto ou isoladamente, levam à sensibilidade alterada dos neurônios nociceptivos, com desenvolvimento de atividade espontânea e exacerbada e, consequentemente, dor espontânea e hiperalgesia. Dentre os mecanismos centrais, a ativação exacerbada de neurônios nociceptivos centrais, a neuroplasticidade, as alterações nas propriedades eletrofisiológicas e a hiperexcitabilidade neuronal, além das modificações nos controles modulatórios da dor, são eventos que levam à instalação e à manutenção da dor. CONCLUSÃO: Diversos mecanismos estão envolvidos nas dores neuropáticas, tanto a nível periférico quanto central, apesar dos eventos específicos da neuralgia do trigêmeo não estarem totalmente elucidados. Estudos que abordem a sua neurobiologia específica são necessários para a compreensão das alterações funcionais e comportamentais presentes, com claras repercussões no tratamento e manuseio clínico da neuralgia do trigêmeo.
ABSTRACT
El dolor agudo postoperatorio constituye un importante desafío para el anestesiólogo y un derecho para los pacientes. No obstante, en la actualidad éste continúa presente en un alto porcentaje de pacientes, a pesar de los esfuerzoz en la difusión de su evaluación y en el uso de diferentes terapias. una importante e interesante forma de cambiar estas cifras puede ser la investigación de la fisiopatología del dolor agudo postoperatorio y la difusión de los resultados. En los últimos años se ha profundizado en el conocimiento de la fisiopatología del dolor agudo postoperatorio, donde se ha determinado que existen cambios capaces de enfrentar la noxa quirúrgica, conocidos como neuroplasticidad, una de cuyas principales expresiones es el mecanismo de sensibilización. Se presenta a continuación una revisión de los principales mecanismos involucrados en el desarrollo y mantención de esta neuroplasticidad.
Accute postoperative pain is a great challenge for anesthesiologists and a right for patients. However, there is still an important percentage of patients with accute postoperative pain, despite all the efforts that have been made to divulge the existing evaluation methods and the use of different therapies. Research of physiopathology of accute postoperative pain might be a relevant and interesting way to change such percentage as well as the publication of the results from that research. In the last years, researchers have gained deeper knowledge in the field of physiopathology of accute postoperative pain and found there are some changes with the capacity to face the surgical noxa known as neuroplasticity, being one of the most important expressions the sensitizazation mechanism. A review of the most important mechanisms that play a part in the development and maintenance of this neuroplasticity is presented below.