Progress of injection sites of local infiltration analgesia in total knee arthroplasty / 中国修复重建外科杂志

OBJECTIVE@#To review the research progress of injection sites of local infiltration analgesia (LIA) in total knee arthroplasty (TKA).@*METHODS@#The relevant domestic and foreign literature in recent years was extensively reviewed. The neuroanatomy of the knee, and the research progress of the selection and the difference of effectiveness between different injection sites of LIA in clinical studies were summarized.@*RESULTS@#Large concentrations of nociceptors are present throughout the various tissues of the knee joint. Patellar tendon, subpatellar fat pad, lateral collateral ligament insertions, iliotibial band insertions, suprapatellar capsule, and posterior capsule were more sensitive to pain. Most current studies support injections into the lateral capsule, collateral ligament, retinaculum, quadriceps tendon, fat pad, and subcutaneous tissue. Whether to inject into the back of the knee and subperiosteum is controversial.@*CONCLUSION@#The relative difference of knee tissue sensitivity to pain has guiding significance for the selection of LIA injection site after TKA. Although researchers have conducted clinical trials on injection site and technique of LIA in TKA, there are certain limitations. The optimal scheme has not been determined yet, and further studies are needed.

Nuclear Factor I/A Controls A-fiber Nociceptor Development / 神经科学通报·英文版

Noxious mechanical information is transmitted through molecularly distinct nociceptors, with pinprick-evoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2 (Npy2r) and von Frey filament-evoked punctate pressure information via unmyelinated C fiber nociceptors marked by MrgprD. However, the molecular programs controlling their development are only beginning to be understood. Here we demonstrate that Npy2r-expressing sensory neurons are in fact divided into two groups, based on transient or persistent Npy2r expression. Npy2r-transient neurons are myelinated, likely including A-fiber nociceptors, whereas Npy2r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb. We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2r-transient A-fiber nociceptors and MrgprD C-fiber nociceptors, respectively. Behaviorally, mice with conditional knockout of Nfia, but not Runx1 showed a marked attenuation of pinprick-evoked nocifensive responses. Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.

Depolarizing Effectors of Bradykinin Signaling in Nociceptor Excitation in Pain Perception

Inflammation is one of the main causes of pathologic pain. Knowledge of the molecular links between inflammatory signals and pain-mediating neuronal signals is essential for understanding the mechanisms behind pain exacerbation. Some inflammatory mediators directly modulate the excitability of pain-mediating neurons by contacting the receptor molecules expressed in those neurons. For decades, many discoveries have accumulated regarding intraneuronal signals from receptor activation through electrical depolarization for bradykinin, a major inflammatory mediator that is able to both excite and sensitize pain-mediating nociceptor neurons. Here, we focus on the final effectors of depolarization, the neuronal ion channels, whose functionalities are specifically affected by bradykinin stimulation. Particular G-protein coupled signaling cascades specialized for each specific depolarizer ion channels are summarized. Some of these ion channels not only serve as downstream effectors but also play critical roles in relaying specific pain modalities such as thermal or mechanical pain. Accordingly, specific pain phenotypes altered by bradykinin stimulation are also discussed. Some members of the effector ion channels are both activated and sensitized by bradykinin-induced neuronal signaling, while others only sensitized or inhibited, which are also introduced. The present overview of the effect of bradykinin on nociceptor neuronal excitability at the molecular level may contribute to better understanding of an important aspect of inflammatory pain and help future design of further research on the components involved and pain modulating strategies.

Neurochemical Properties of Dental Primary Afferent Neurons

The long belief that dental primary afferent (DPA) neurons are entirely composed of nociceptive neurons has been challenged by several anatomical and functional investigations. In order to characterize non-nociceptivepopulation among DPA neurons, retrograde transport fluorescent dye was placed in upper molars of rats and immunohistochemical detection of peripherin and neurofilament 200 in the labeled trigeminal ganglia was performed. As the results, majority ofDPA neurons were peripherin-expressing small-sized neurons, showing characteristic ofnociceptive C-fibers. However, 25.7% of DPA were stained with antibody against neurofilament 200, indicating significant portion of DPA neurons are related to large myelinated Abeta fibers. There were a small number of neurons thatexpressed both peripherin and neurofilament 200, suggestive of Adelta fibers. The possible transition of neurochemical properties by neuronal injury induced by retrograde labeling technique was ruled out by detection of minimal expression of neuronal injury marker, ATF-3. These results suggest that in addition to the large population of C-fiber-related nociceptive neurons, a subset of DPA neurons is myelinated large neurons, which is related to low-threshold mechanosensitive Abeta fibers. We suggest that these Abeta fiber-related neurons might play a role as mechanotransducers of fluid movement within dentinal tubules.

Transient Receptor Potential (TRP) Channels / 대한이비인후과학회지

Transient receptor potential (TRP) protein is a superfamily of cation channels which have 6 transmembrane domains and mainly pass calcium ion through themselves. There are seven types of subfamilies in the TRP superfamily. TRP channels can be activated by various kinds of stimuli. Some TRP channels are polymodal receptors because two or more types of stimuli can activate the same type of TRP channels. TRP proteins can play roles in a living organism as receptors for sensing outside stimuli or inside local stimuli of itself, as signal conductors, or as signal transducers. Especially, TRP channels have key roles in thermosensation, mechanosensation, taste, trigeminal olfaction and nociception. Therefore, TRP channels can be important subjects of research in ENT field.

Neuroplasticidad y dolor / Neuroplasticity and pain

Todas las formas de dolor incluyen el desarrollo de un estado de hiperalgesia que ilustra la naturaleza dinámica y plástica de la sensación de dolor. La hiperalgesia es la característica más importante del proceso doloroso y es la expresión de la hipersensibilidad de las vías del dolor inducida por la sensibilización de los receptores periféricos que registran eventos dolorosos y de las neuronas que transmiten y procesan esta información sensorial al SNC. Los nociceptores periféricos se sensibilizan adquiriendo una mayor y a veces nueva capacidad de respuesta a los estímulos periféricos. Por otra parte, un proceso de plasticidad sináptica, del cual se ha identificado una variedad de componentes moleculares, interviene en la amplificación central de las señales de las aferencias nociceptivas, lo cual evoca la hipersensibilidad de las neuronas centrales. El resultado final es un proceso sensorial que, a pesar de haber sido puesto en marcha inicialmente por una lesión, puede no mantener una relación estrecha con la lesión original y convertirse en un estado de dolor crónico sin tener una causa definida.

All froms of pain include the development of a hyperalgesic state that illustrates the dynamic and plastic nature of pain sesation. Hyperalgesia is the most prominent feature of the pain process and is the expression of hypersensitivity of the pain pathway induced by the sensitization of the peripheral receptors that signal painful events and of the neurons that transmit and process this sensory information to the CNS. Peripheral nociceptors can be sensitized, acquiring enhanced, and sometimes novel, responsiveness to peripheral stimuli. On the other hand a process of synaptic plasticity, of which several molecular components have already been identified, mediates the central amplification of the afferent signals that leads to the hypersensitivity of central neurons. The final result is a sensory process that, although initially triggered by injury, may not keep a close relationship with the originating injury and develop into a chronic pain state in the absence of a defined cause.

Pathophysiology of Pain

Pain is a sensation induced by activation of the peripheral nociceptors when tissue is damaged by direct stimuli or has a possibility of damage. There exist nociceptors for detecting the noxious stimuli in periphery, and the nociceptive informations were transmitted via A delta- or C-fibers. Acute pain is caused by direct noxious stimuli, and chronic pains are produced by inflammation or nerve damage. The mechanisms of chronic pains are associated with the changes of cen-tral nervous system (CNS) as well as those in peripheral nocicpetors. Immune cells and neurotrophins are also involved in the mechanisms of chronic pain. Recently, there has been a tendency among pain researchers that chronic pain might be explained the plastic changes in the nociceptive synaptic transmission through the spinal cord. These are associated with changes in intracellular Ca(2+)concentration, subsequent intracellular signal transduction pathways, which result in changes in AMPA receptor dynamics. This sequential changes may induce allodynia and hyperalgesia observed in chronic pain patients. This review suggests new interpretation for pain mechanism and new approach for chronic pain.

Adrenergic sensitivity of uninjured C-fiber nociceptors in neuropathic rats

We investigated the adrenergic sensitivity of afferent fibers in the L4 dorsal roots of rats with a unilateral ligation of the L5-L6 spinal nerves. About 12% of nociceptive fibers on the affected side were excited by sympathetic stimulation or by intra-arterial injection of norepinephrine which did not affect A beta-fiber activity. Sympathetic excitation of nociceptive fibers was suppressed by alpha 1-antagonist prazosin, while it was unaffected by alpha 2-antagonist yohimbine. Most of these fibers were excited by intra-arterial injection of alpha 1-agonist phenylephrine, without being affected by an injection of alpha 2-agonist clonidine. Sympathetic excitation was blocked by lidocaine applied near the receptive fields of recorded fibers. The results suggested that some nociceptors remaining intact after partial nerve injury become sensitive to sympathetic activity by the mediation of alpha 1-adrenoceptors in the peripheral endings.

Effects of somatostatin and morphine on the responses of dorsal horn neurons to noxious peripheral nerve stimulation in cats

Painful nociceptive informations are well known to be transferred from nociceptors through spinal dorsal horn not only in different pathways but also in diverse nature depending on the type of noxious stimuli. There have been some controversies about the role of neuropeptide somatostatin in the transmission of the nociceptive information to the dorsal horn cells of the spinal cord. We performed the study in order to elucidate the effects of somatostatin on transmission of noxious stimuli in the spinal dorsal horn, comparing with those of morphine. Using carbon-filamented microelectrode, the single cell activities of wide dynamic range(WDR) neuron were recorded extracellularly at the lumbosacral enlargement of the spinal cord in cats after noxious mechanical(squeeze), thermal(heat lamp), and cold(dry ice) stimulation to the receptive field. The sciatic nerve was stimulated electrically to evoke, A4-fiber and C-fiber each other. Data were compiled into single pass time histograms or postsimulus time histograms. Twenty micro-gram of somatostatin was injected intravenously to study the changes of single cell activities in 20 minutes, which were compared with the effects of morphine(2m/kg). Then naloxone was administrated(0.1mg/kg) to know whether it antagonized the effects of somatostatin and morphine And those finding were also observed in inverted WDR cells. In WDR cell, somatostain decreased the cellular responses to noxious heat stimuli in 6cell(n=9), but increased those to cold stimuli in 4 cells(n=6). And the responses to noxious mechanical stimuli were so diverse that they were slightly increased in 7 cells(164%), decreased in 5 cells, and were not changed in 6 cells(n=18). A-response, the response to peripheral Ad-afferent activation, showed a tendency to be facilitated(n=6/9), while C-response had a slightly depressed tendency(n=4/9). Morphine strongly suppressed the responses of dorsal horn neurons to noxious heat(n=9/13), cold(n=2/2), mechanical stimuli(n=16/19) and electrical A-response(n=7/10), C-response(n=6/7). Following subsequent injection of naloxone, the effects of morphine on noxious stimuli evoked response were fully reversed but those of somatostatin were not antagonized. There was significant difference between the reversal effects of naloxone on morphine and somatostatin(p<0.05). From the above results it is concluded that somatostatin suppresses the transmission of nociceptive heat stimuli, especially via C-fiber, while facilitates that of nociceptive mechanical and cold stimuli via Adelta-fiber in spinal dorsal horn cells. Also the somatostatin appears to have different nociceptive mechanism from morphine.

Human Cutaneous Nociceptive Afferents with Unmyelinated (C), and myelinated (Aδ) fibers / 全日本鍼灸学会雑誌

Inserting a tangusten microelectrode into the peroneous nerve of the conscious human subject, the authors recorded the discharge of primary afferent C and A δ fibers. Most of the C fibers belonged to the polymodal group, as these were excited by both mechanical and thermal stimulations. These units responded to painful mechanical or thermal stimuli, as well as to non-painful stimuli of these modalities. These polymodal receptors were capable of responding to a wide range of stimulation intensity.<br>Only some of the Aδ fibers responded to mechanical stimulation of a high intensity and painful thermal stimulation. These units increased their discharge to repeated heat administration showing a marked sensitization. This sensitization corresponded to the sense of increased heat experience by the human subjects who had hyperalgesia from the increasing heat. These findings indicate that these Aδ afferent fibers transmit sensation of hyperalgesia from the hairy skin to the higher centers.