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Query: UMLS:C0030193 (pain)
 261,466 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Nerve growth factor (NGF) is a well-known neurotrophic factor essential for the survival and maintenance of sensory and sympathetic neurons. Congenital insensitivity to pain with anhidrosis (CIPA) is a genetic disorder due to loss-of-function mutations in the NTRK1 (also known as TRKA) gene encoding TrkA, a receptor tyrosine kinase for NGF. Patients with CIPA provide us a rare opportunity to explore the developmental and physiological function of the NGF-dependent neurons in behavior, cognitive, and mental activities that are not available in animal studies. Here, I discuss the significance of findings that patients with CIPA lack NGF-dependent neurons, including interoceptive polymodal receptors, sympathetic postganglionic neurons, and probably several types of neurons in the brain. They also exhibit characteristic emotional behavior or problems. Together, the NGF-TrkA system is essential for the establishment of a neural network for interoception and homeostasis that may underlie 'gut feelings'. Thus, NGF-dependent neurons play a crucial role in emotional experiences and decision-making processes. Prospective studies focused on these neurons might provide further insights into the neural basis of human emotion and feeling.
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PMID:Nerve growth factor, interoception, and sympathetic neuron: lesson from congenital insensitivity to pain with anhidrosis. 1920 60

Neurotrophic factors (NTFs), beside regulating neuronal survival in the central and peripheral nervous system, are also involved in the modulation of neuronal function in the adult animal. Both brain-derived neurotrophic factor (BDNF) and glial cell-derived neurotrophic factor (GDNF) levels are altered in pathological pain states, and exogenous BDNF and GDNF have multiple effects on pain behavior, depending on the animal model (i.e. inflammatory vs. neuropathic). Thermally gated TRP channels TRPM8, TRPA1 and TRPV1 play a significant role in pain signaling and their pattern and level of expression as well as their biophysical properties are altered in chronic pain states. Our aim was to investigate the effect of long-term and acute exposure to BDNF and GDNF on the functional expression of these thermoTRP channels in cultured rat dorsal root ganglion (DRG) neurons. We found that while BDNF treatment primarily increased the fraction of capsaicin-sensitive (TRPV1-expressing) neurons, GDNF exposure led to an increase in the allyl isothiocyanate (AITC)-responding (TRPA1-expressing) population. Moreover, BDNF treatment increased the amplitude of the response to both AITC and capsaicin. Acute treatment with both NTFs leads to a reduction in the magnitude of tachyphylaxis to noxious stimuli (heat and AITC). Overall, our data provides evidence for a role of BDNF and GDNF in regulating the pattern of expression and level of activity of the transducer channels TRPA1 and TRPV1, leading to enhanced neuronal sensitivity to painful stimuli and increased co-expression of thermoTRP channels.
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PMID:Acute and chronic effects of neurotrophic factors BDNF and GDNF on responses mediated by thermo-sensitive TRP channels in cultured rat dorsal root ganglion neurons. 1952 60

Previous data show that spinal cord long-term potentiation (LTP) can be induced by electrical high-frequency stimulation (HFS) conditioning applied to the sciatic nerve. It has been suggested that the cellular events leading to this form of plasticity may contribute to central hyperalgesia. In the present study, extracellular recordings from single dorsal horn neurons and quantitative real-time reverse-transcriptase polymerase chain reaction (RT-PCR) on rat dorsal horn tissue were used to examine whether maintenance of spinal LTP is associated with changes in gene expression of the proinflammatory interleukin-1beta (IL-1beta), glial cell-line derived neurotrophic factor (GDNF), inducible nitric oxide synthase (iNOS), p38 mitogen-activated protein kinase (p38 MAPK), cyclooxygenase 2 (COX2) and tumor necrosis factor alpha (TNFalpha). The data demonstrated that the HFS conditioning induced a robust increase in the dorsal horn C-fibre responses, which outlasted the duration of the experiments of 6h (p<0.05, HFS vs. control). Moreover, a significant increase in the expression of mRNA for IL-1beta, GDNF and iNOS were observed 6h following the HFS conditioning (p<0.05, HFS vs. control). For the first time we show that spinal cord LTP is associated with an increased dorsal horn expression of the genes for IL-1beta, GDNF and iNOS.
Eur J Pain 2010 Mar
PMID:Spinal cord long-term potentiation (LTP) is associated with increased dorsal horn gene expression of IL-1beta, GDNF and iNOS. 1959 10

The afferent innervation of the urinary bladder consists primarily of small myelinated (Adelta) and unmyelinated (C-fiber) axons that respond to chemical and mechanical stimuli. Immunochemical studies indicate that bladder afferent neurons synthesize several putative neurotransmitters, including neuropeptides, glutamic acid, aspartic acid, and nitric oxide. The afferent neurons also express various types of receptors and ion channels, including transient receptor potential channels, purinergic, muscarinic, endothelin, neurotrophic factor, and estrogen receptors. Patch-clamp recordings in dissociated bladder afferent neurons and recordings of bladder afferent nerve activity have revealed that activation of many of these receptors enhances neuronal excitability. Afferent nerves can respond to chemicals present in urine as well as chemicals released in the bladder wall from nerves, smooth muscle, inflammatory cells, and epithelial cells lining the bladder lumen. Pathological conditions alter the chemical and electrical properties of bladder afferent pathways, leading to urinary urgency, increased voiding frequency, nocturia, urinary incontinence, and pain. Neurotrophic factors have been implicated in the pathophysiological mechanisms underlying the sensitization of bladder afferent nerves. Neurotoxins such as capsaicin, resiniferatoxin, and botulinum neurotoxin that target sensory nerves are useful in treating disorders of the lower urinary tract.
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PMID:Afferent nerve regulation of bladder function in health and disease. 1965 6

Following surgery, nerve injury can lead to persistent neuropathic pain. Pre-emptive and preventive analgesic treatments in the perioperative period aim to minimize nerve injury-induced pain. Here we demonstrate that a perioperative regimen of amitriptyline (10 mg/kg i.p. 30 min before and immediately after surgery, followed by oral amitriptyline 15-18 mg/kg/day in the drinking water for 7 days post-surgery) prevents hypersensitivity to a chemogenic stimulus (alphabeta-MeATP, a ligand for P2X3 receptors, together with noradrenaline or NA) in the spared nerve injury (SNI) model in rats. It also prevents hyposensitivity to capsaicin and NA. However, amitriptyline treatment had no effect on the development of mechanical allodynia. We investigated the role of NA mechanisms in the action of amitriptyline by using the neurotoxin 6-hydroxydopamine (6-OHDA) and by examining desipramine. Intrathecal treatment with 6-OHDA on the day of surgery reversed the preventive effect of amitriptyline on hypersensitivity to alphabeta-MeATP/NA, and desipramine exhibited a similar effect to amitriptyline. We also examined the effect of antibodies to the nerve growth factors glial-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), given intrathecally three times (days 0, 3 and 7) on the action of amitriptyline and observed that the interruption of GDNF and BDNF signaling impaired the prevention of hypersensitivity to alphabeta-MeATP/NA. This study indicates that tricyclic antidepressants given in the perioperative period may be useful in preventing nerve injury-induced sensory changes that contribute to the development of chronic post-surgical neuropathic pain.
Pain 2009 Dec
PMID:Perisurgical amitriptyline produces a preventive effect on afferent hypersensitivity following spared nerve injury. 1974 84

C-fiber sensory neurons comprise nociceptors and smaller populations of cells detecting innocuous thermal and light tactile stimuli. Markers identify subpopulations of these cells, aiding our understanding of their physiological roles. The transient receptor potential vanilloid 1 (TRPV1) cation channel is characteristic of polymodal C-fiber nociceptors and is sensitive to noxious heat, irritant vanilloids, and protons. By using immunohistochemistry, in situ hybridization, and retrograde tracing, we anatomically characterize a small subpopulation of C-fiber cells that express high levels of TRPV1 (HE TRPV1 cells). These cells do not express molecular markers normally associated with C-fiber nociceptors. Furthermore, they express a unique complement of neurotrophic factor receptors, namely, the trkC receptor for neurotrophin 3, as well as receptors for neurturin and glial cell line-derived neurotrophic factor. HE TRPV1 cells are distributed in sensory ganglia throughout the neuraxis, with higher numbers noted in the sixth lumbar ganglion. In this ganglion and others of the lumbar and sacral regions, 75% or more of such HE TRPV1 cells express estrogen receptor alpha, suggestive of their regulation by estrogen and a role in afferent sensation related to reproduction. Afferents from these cells provide innervation to the hairy skin of the perineal region and can be activated by thermal stimuli from 38 degrees C, with a maximal response at 42 degrees C, as indicated by induction of extracellular signal-regulated kinase phosphorylation. We hypothesize that apart from participating in normal thermal sensation relevant to thermoregulation and reproductive functions, HE TRPV1 cells may mediate burning pain in chronic pain syndromes with perineal localization.
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PMID:Identification of perineal sensory neurons activated by innocuous heat. 1993 7

Chronic pancreatitis is a state of chronic inflammation characterized by progressive destruction of the pancreas. Pancreatic pain, a cardinal symptom in chronic pancreatitis patients has always been a subject of great interest and controversy. The precise mechanism of pain and its persistence in chronic pancreatitis patients remain unknown. Several pancreatic, neurogenic and central hypotheses have been proposed for the pathogenesis of pain. In patients with a dilated main pancreatic duct, increased intraductal pressure due to strictures/calculi, presence of interstitial hypertension, pancreatic ischemia and fibrosis and pseudocyst have been proposed to contribute to chronic pain. "Neurogenic" or "neuropathic" theory is based on the fact that patients with chronic pancreatitis have enlarged intrapancreatic nerves with microscopic damage to nerve sheaths (mediated by growth-associated protein 43 (GAP-43), that makes them more susceptible to mediators like brain derived neurotrophic factor, nerve growth factor and TrkA and artemin, the expression of which directly correlates with severity of pain frequency and intensity. The central theory proposes that reorganization of neurons in the insula may explain the chronic pain in these patients. However all these studies have been observational. Further studies are required in the future to characterize these immune response observed in the intrapancreatic neurons in chronic pancreatitis and the neuronal changes in the brain if we are to manage these patients with chronic pain and give them a better quality of life.
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PMID:Recent advancements in the pathogenesis of pain in chronic pancreatitis: the argument continues. 2019 Jul 25

Small unmyelinated sensory neurons classified as nociceptors are divided into two subpopulations based on phenotypic differences, including expression of neurotrophic factor receptors. Approximately half of unmyelinated nociceptors express the NGF receptor TrkA, and half express the GDNF family ligand (GFL) receptor Ret. The function of NGF/TrkA signaling in the TrkA population of nociceptors has been extensively studied, and NGF/TrkA signaling is a well established mediator of pain. The GFLs are analgesic in models of neuropathic pain emphasizing the importance of understanding the physiological function of GFL/Ret signaling in nociceptors. However, perinatal lethality of Ret-null mice has precluded the study of the physiological role of GFL/Ret signaling in the survival, maintenance, and function of nociceptors in viable mice. We deleted Ret exclusively in nociceptors by crossing nociceptor-specific Na(v)1.8 Cre and Ret conditional mice to produce Ret-Na(v)1.8 conditional knock-out (CKO) mice. Loss of Ret exclusively in nociceptors results in a reduction in nociceptor number and size, indicating that Ret signaling is important for the survival and trophic support of these cells. Ret-Na(v)1.8 CKO mice exhibit reduced epidermal innervation but normal central projections. In addition, Ret-Na(v)1.8 CKO mice have increased sensitivity to cold and increased formalin-induced pain, demonstrating that Ret signaling modulates the function of nociceptors in vivo. Enhanced inflammation-induced pain may be mediated by decreased prostatic acid phosphatase (PAP), as PAP levels are markedly reduced in Ret-Na(v)1.8 CKO mice. The results of this study identify the physiological role of endogenous Ret signaling in the survival and function of nociceptors.
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PMID:RET signaling is required for survival and normal function of nonpeptidergic nociceptors. 2023 69

In spite of the fact that brain derived neurotrophic factor (BDNF) has been reported to be implicated in the development of visceral pain, it remains to be determined whether the role of BDNF in pain is gender dependent. The present study investigated the effect of BDNF on visceral pain in different gender rats. A model for visceral pain was established by intraperitoneal (i.p.) injection of acetic acid (AA) into Sprague-Dawley rats: males, females and females with an ovariectomy (OVX). The pain behavior index was assessed by counting the number of abdominal contractions for 60min after i.p. injection of AA. Anti-BDNF antibody, or BDNF, was administered 1h before the AA injection to examine the role of BDNF in visceral pain. After the AA injection, the number of abdominal contraction was dramatically increased in all rats but females showed more severe pain behavior than males. The higher sensitivity to AA-induced nocifensive response was attenuated by OVX. Pretreatment with anti-BDNF antibody significantly exacerbated the nocifensive response in males but attenuated it in females. While exogenous BDNF administration did not alter AA injection-induced nocifensive response in females, BDNF pretreatment attenuated the nocifensive response in males but exacerbated it in females with OVX. The present study suggests there is a gender dichotomy in visceral pain induced by AA injection. In addition, the modulation of visceral pain by BDNF is also sex dependent, i.e., BDNF facilitates the visceral pain in female rats but displays an opposite effect in male rats. Our results may have important implications in the management of clinical pain.
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PMID:Sex-differential modulation of visceral pain by brain derived neurotrophic factor (BDNF) in rats. 2047 Aug 67

Peripheral nerve injury activates spinal microglia. This leads to enduring changes in the properties of dorsal horn neurons that initiate central sensitization and the onset of neuropathic pain. Although a variety of neuropeptides, cytokines, chemokines and neurotransmitters have been implicated at various points in this process, it is possible that much of the information transfer between activated microglia and neurons, at least in this context, may be explicable in terms of the actions of brain derived neurotrophic factor (BDNF). Microglial-derived BDNF mediates central sensitization in lamina I by attenuating inhibitory synaptic transmission. This involves an alteration in the chloride equilibrium potential as a result of down regulation of the potassium-chloride exporter, KCC2. In lamina II, BDNF duplicates many aspects of the effects of chronic constriction injury (CCI) of the sciatic nerve on excitatory transmission. It mediates an increase in synaptic drive to putative excitatory neurons whilst reducing that to inhibitory neurons. CCI produces a specific pattern of changes in excitatory synaptic transmission to tonic, delay, phasic, transient and irregular neurons. A very similar 'injury footprint' is seen following long-term exposure to BDNF. This review presents new information on the action of BDNF and CCI on lamina II neurons, including the similarity of their actions on the kinetics and distributions of subpopulations of miniature excitatory postsynaptic currents (mEPSC). These findings raise the possibility that BDNF functions as a final common path for a convergence of perturbations that culminate in the generation of neuropathic pain.
Mol Pain 2010 Jul 23
PMID:Is BDNF sufficient for information transfer between microglia and dorsal horn neurons during the onset of central sensitization? 2065 59


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