Inhibition of p38-MAPK signaling pathway attenuates breast cancer induced bone pain and disease progression in a murine model of cancer-induced bone pain.


BACKGROUND:Mechanisms driving cancer-induced bone pain are poorly understood. A central factor implicated to be a key player in the process of tumorigenesis, osteoclastogenesis and nociception is p38 MAPK. We determined the role of p38 MAPK in a mouse model of breast cancer induced bone pain in which mixed osteolytic and osteoblastic remodeling occurs. RESULTS:In cancer-treated mice, acute as well as chronic inhibition of p38 MAPK with SB203580 blocked flinching and guarding behaviors in a dose-dependent manner whereas no effect on thresholds to tactile stimuli was observed. Radiographic analyses of bones demonstrated that chronic inhibition of p38 MAPK reduced bone loss and incidence of spontaneous fracture in cancer-treated mice. Histological analysis of bones collected from mice treated with the p38 MAPK inhibitor showed complete absence of osteoblastic growth in the intramedullary space as well as significantly reduced tumor burden. CONCLUSIONS:Blockade of non-evoked pain behaviors but not hypersensitivity suggests differences in the underlying mechanisms of specific components of the pain syndrome and a possibility to individualize aspects of pain management. While it is not known whether the role of p38 MAPK signaling can be expanded to other cancers, the data suggest a need for understanding molecular mechanisms and cellular events that initiate and maintain cancer-induced bone pain for effective management for both ongoing pain as well as breakthrough pain.


Mol Pain


Molecular pain


Sukhtankar D,Okun A,Chandramouli A,Nelson MA,Vanderah TW,Cress AE,Porreca F,King T




Has Abstract


2011-10-20 00:00:00










  • P2X4-receptor participates in EAAT3 regulation via BDNF-TrkB signaling in a model of trigeminal allodynia.

    abstract::Objective Previous studies of neuropathic pain have suggested that the P2X4 purinoceptor (P2X4R) in spinal microglia is essential for maintaining allodynia following nerve injury. However, little is known about its role in inflammatory soup-induced trigeminal allodynia, which closely mimics chronic migraine status. He...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Liu C,Zhang Y,Liu Q,Jiang L,Li M,Wang S,Long T,He W,Kong X,Qin G,Chen L,Zhang Y,Zhou J

    更新日期:2018-01-01 00:00:00

  • Novel SCN9A missense mutations contribute to congenital insensitivity to pain: Unexpected correlation between electrophysiological characterization and clinical phenotype.

    abstract::Congenital insensitivity to pain (OMIM 243000) is an extremely rare disorder caused by loss-of-function mutations in SCN9A encoding Nav1.7. Although the SCN9A mutations and phenotypes of painlessness and anosmia/hyposmia in patients are previously well documented, the complex relationship between genotype and phenotyp...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Sun J,Li L,Yang L,Duan G,Ma T,Li N,Liu Y,Yao J,Liu JY,Zhang X

    更新日期:2020-01-01 00:00:00

  • TRPV1 gain-of-function mutation impairs pain and itch sensations in mice.

    abstract::Transient receptor potential vanilloid 1 (TRPV1) is a non-selective cation channel, which can detect various noxious stimuli that cause pain, inflammation, hyperalgesia, and itch. TRPV1 knock-out mice show deficiency in nociception, but the in vivo effects of persistent activation of TRPV1 are not completely understoo...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Duo L,Hu L,Tian N,Cheng G,Wang H,Lin Z,Wang Y,Yang Y

    更新日期:2018-01-01 00:00:00

  • Novel expression pattern of neuropeptide Y immunoreactivity in the peripheral nervous system in a rat model of neuropathic pain.

    abstract:BACKGROUND:Neuropeptide Y (NPY) has been implicated in the modulation of pain. Under normal conditions, NPY is found in interneurons in the dorsal horn of the spinal cord and in sympathetic postganglionic neurons but is absent from the cell bodies of sensory neurons. Following peripheral nerve injury NPY is dramaticall...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Magnussen C,Hung SP,Ribeiro-da-Silva A

    更新日期:2015-05-27 00:00:00

  • Mycolactone-mediated neurite degeneration and functional effects in cultured human and rat DRG neurons: Mechanisms underlying hypoalgesia in Buruli ulcer.

    abstract:BACKGROUND:Mycolactone is a polyketide toxin secreted by the mycobacterium Mycobacterium ulcerans, responsible for the extensive hypoalgesic skin lesions characteristic of patients with Buruli ulcer. A recent pre-clinical study proposed that mycolactone may produce analgesia via activation of the angiotensin II type 2 ...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Anand U,Sinisi M,Fox M,MacQuillan A,Quick T,Korchev Y,Bountra C,McCarthy T,Anand P

    更新日期:2016-06-20 00:00:00

  • The mu opioid agonist morphine modulates potentiation of capsaicin-evoked TRPV1 responses through a cyclic AMP-dependent protein kinase A pathway.

    abstract:BACKGROUND:The vanilloid receptor 1 (TRPV1) is critical in the development of inflammatory hyperalgesia. Several receptors including G-protein coupled prostaglandin receptors have been reported to functionally interact with the TRPV1 through a cAMP-dependent protein kinase A (PKA) pathway to potentiate TRPV1-mediated c...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Vetter I,Wyse BD,Monteith GR,Roberts-Thomson SJ,Cabot PJ

    更新日期:2006-07-16 00:00:00

  • Expression of inwardly rectifying potassium channels by an inducible adenoviral vector reduced the neuronal hyperexcitability and hyperalgesia produced by chronic compression of the spinal ganglion.

    abstract:BACKGROUND:A chronic compressed dorsal root ganglion (CCD) in rat produces pain behavior and an enhanced excitability of neurons within the compressed ganglion. Kir2.1 is an inwardly rectifying potassium channel that acts to stabilize the resting potential of certain cell types. We hypothesized that an inducible expres...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Ma C,Rosenzweig J,Zhang P,Johns DC,LaMotte RH

    更新日期:2010-10-06 00:00:00

  • Peripheral KV7 channels regulate visceral sensory function in mouse and human colon.

    abstract::Background Chronic visceral pain is a defining symptom of many gastrointestinal disorders. The KV7 family (KV7.1-KV7.5) of voltage-gated potassium channels mediates the M current that regulates excitability in peripheral sensory nociceptors and central pain pathways. Here, we use a combination of immunohistochemistry,...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Peiris M,Hockley JR,Reed DE,Smith ESJ,Bulmer DC,Blackshaw LA

    更新日期:2017-01-01 00:00:00

  • TRPV3 and TRPV4 ion channels are not major contributors to mouse heat sensation.

    abstract:BACKGROUND:The discovery of heat-sensitive Transient Receptor Potential Vanilloid (TRPV) ion channels provided a potential molecular explanation for the perception of innocuous and noxious heat stimuli. TRPV1 has a significant role in acute heat nociception and inflammatory heat hyperalgesia. Yet, substantial innocuous...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Huang SM,Li X,Yu Y,Wang J,Caterina MJ

    更新日期:2011-05-17 00:00:00

  • Gabapentin reverses central hypersensitivity and suppresses medial prefrontal cortical glucose metabolism in rats with neuropathic pain.

    abstract:BACKGROUND:Gabapentin (GBP) is known to suppress neuropathic hypersensitivity of primary afferents and the spinal cord dorsal horn. However, its supra-spinal action sites are unclear. We identify the brain regions where GBP changes the brain glucose metabolic rate at the effective dose that alleviates mechanical allody...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Lin HC,Huang YH,Chao TH,Lin WY,Sun WZ,Yen CT

    更新日期:2014-09-25 00:00:00

  • Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain.

    abstract::Neuropathic pain is a debilitating clinical condition with few efficacious treatments, warranting development of novel therapeutics. We hypothesized that dysregulated translation regulation pathways may underlie neuropathic pain. Peripheral nerve injury induced reorganization of translation machinery in the peripheral...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Melemedjian OK,Asiedu MN,Tillu DV,Sanoja R,Yan J,Lark A,Khoutorsky A,Johnson J,Peebles KA,Lepow T,Sonenberg N,Dussor G,Price TJ

    更新日期:2011-09-21 00:00:00

  • Involvement of peripheral ionotropic glutamate receptors in orofacial thermal hyperalgesia in rats.

    abstract:BACKGROUND:The purpose of the present study was to elucidate the mechanisms that may underlie the sensitization of trigeminal spinal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) neurons to heat or cold stimulation of the orofacial region following glutamate (Glu) injection. RESULTS:Glu application t...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Honda K,Noma N,Shinoda M,Miyamoto M,Katagiri A,Kita D,Liu MG,Sessle BJ,Yasuda M,Iwata K

    更新日期:2011-09-28 00:00:00

  • Streptozotocin-induced early thermal hyperalgesia is independent of glycemic state of rats: role of transient receptor potential vanilloid 1(TRPV1) and inflammatory mediators.

    abstract:BACKGROUND:Streptozotocin (STZ) is used as a common tool to induce diabetes and to study diabetes-induced complications including diabetic peripheral neuropathy (DPN). Previously, we have reported that STZ induces a direct effect on neurons through expression and function of the Transient receptor potential vanilloid 1...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Bishnoi M,Bosgraaf CA,Abooj M,Zhong L,Premkumar LS

    更新日期:2011-07-27 00:00:00

  • Modulation of chloride homeostasis by inflammatory mediators in dorsal root ganglion neurons.

    abstract:BACKGROUND:Chloride currents in peripheral nociceptive neurons have been implicated in the generation of afferent nociceptive signals, as Cl- accumulation in sensory endings establishes the driving force for depolarizing, and even excitatory, Cl- currents. The intracellular Cl- concentration can, however, vary consider...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Funk K,Woitecki A,Franjic-Würtz C,Gensch T,Möhrlen F,Frings S

    更新日期:2008-08-12 00:00:00

  • Reduction of voltage gated sodium channel protein in DRG by vector mediated miRNA reduces pain in rats with painful diabetic neuropathy.

    abstract:BACKGROUND:Painful neuropathy is a common complication of diabetes. Previous studies have identified significant increases in the amount of voltage gated sodium channel isoforms Na(V)1.7 and Na(V)1.3 protein in the dorsal root ganglia (DRG) of rats with streptozotocin (STZ)-induced diabetes. We found that gene transfer...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Chattopadhyay M,Zhou Z,Hao S,Mata M,Fink DJ

    更新日期:2012-03-22 00:00:00

  • Neuronal cell lines as model dorsal root ganglion neurons: A transcriptomic comparison.

    abstract:BACKGROUND:Dorsal root ganglion neuron-derived immortal cell lines including ND7/23 and F-11 cells have been used extensively as in vitro model systems of native peripheral sensory neurons. However, while it is clear that some sensory neuron-specific receptors and ion channels are present in these cell lines, a systema...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Yin K,Baillie GJ,Vetter I

    更新日期:2016-04-29 00:00:00

  • Dehydrocorydaline attenuates bone cancer pain by shifting microglial M1/M2 polarization toward the M2 phenotype.

    abstract::Bone cancer pain remains a major challenge in patients with primary or metastatic bone cancer due to a lack of understanding the mechanisms. Previous studies have revealed the two distinct functional polarization states of microglia (classically activated M1 and alternatively activated M2) in the spinal cord in nerve ...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Huo W,Zhang Y,Liu Y,Lei Y,Sun R,Zhang W,Huang Y,Mao Y,Wang C,Ma Z,Gu X

    更新日期:2018-01-01 00:00:00

  • Kinin B1 receptors contributes to acute pain following minor surgery in humans.

    abstract:BACKGROUND:Kinins play an important role in regulation of pain and hyperalgesia after tissue injury and inflammation by activating two types of G-protein-coupled receptors, the kinin B1 and B2 receptors. It is generally accepted that the B2 receptor is constitutively expressed, whereas the B1 receptor is induced in res...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Hamza M,Wang XM,Adam A,Brahim JS,Rowan JS,Carmona GN,Dionne RA

    更新日期:2010-02-13 00:00:00

  • Sigma-1 receptor expression in sensory neurons and the effect of painful peripheral nerve injury.

    abstract:BACKGROUND:The sigma-1 receptor (σ1R), an endoplasmic reticulum chaperone protein, is widely distributed and regulates numerous intracellular processes in neurons. Nerve injury alters the structure and function of axotomized dorsal root ganglion (DRG) neurons, contributing to the development of pain. The σ1R is enriche...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Bangaru ML,Weihrauch D,Tang QB,Zoga V,Hogan Q,Wu HE

    更新日期:2013-09-10 00:00:00

  • Cannabinoid 1 receptor knockout mice display cold allodynia, but enhanced recovery from spared-nerve injury-induced mechanical hypersensitivity.

    abstract:BACKGROUND:The function of the Cannabinoid 1 receptor (CB1R) in the development of neuropathic pain is not clear. Mounting evidence suggest that CB1R expression and activation may contribute to pain. Cannabinoid 1 receptor knockout mice (CB1R-/-) generated on a C57Bl/6 background exhibit hypoalgesia in the hotplate ass...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Sideris A,Piskoun B,Russo L,Norcini M,Blanck T,Recio-Pinto E

    更新日期:2016-05-20 00:00:00

  • Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain.

    abstract::Chemotherapy-induced peripheral neuropathy (CIPN) is an adverse side effect of many anti-cancer chemotherapeutic treatments. CIPN often causes neuropathic pain in extremities, and oxidative stress has been shown to be a major contributing factor to this pain. In this study, we determined the site of oxidative stress a...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Shim HS,Bae C,Wang J,Lee KH,Hankerd KM,Kim HK,Chung JM,La JH

    更新日期:2019-01-01 00:00:00

  • Temperature dependence of erythromelalgia mutation L858F in sodium channel Nav1.7.

    abstract:BACKGROUND:The disabling chronic pain syndrome erythromelalgia (also termed erythermalgia) is characterized by attacks of burning pain in the extremities induced by warmth. Pharmacological treatment is often ineffective, but the pain can be alleviated by cooling of the limbs. Inherited erythromelalgia has recently been...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Han C,Lampert A,Rush AM,Dib-Hajj SD,Wang X,Yang Y,Waxman SG

    更新日期:2007-01-19 00:00:00

  • Do motor control genes contribute to interindividual variability in decreased movement in patients with pain?

    abstract:BACKGROUND:Because excessive reduction in activities after back injury may impair recovery, it is important to understand and address the factors contributing to the variability in motor responses to pain. The current dominant theory is the "fear-avoidance model", in which the some patients' heightened fears of further...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Mishra BK,Wu T,Belfer I,Hodgkinson CA,Cohen LG,Kiselycznyk C,Kingman A,Keller RB,Yuan Q,Goldman D,Atlas SJ,Max MB

    更新日期:2007-07-26 00:00:00

  • Differential contributions of vasopressin V1A and oxytocin receptors in the amygdala to pain-related behaviors in rats.

    abstract::Neuroplastic changes in the amygdala account for emotional-affective aspects of pain and involve neuropeptides such as calcitonin gene-related peptide and corticotropin-releasing factor. Another neuropeptide system, central arginine vasopressin, has been implicated in neuropsychiatric disorders, but its role in pain-r...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Cragg B,Ji G,Neugebauer V

    更新日期:2016-11-11 00:00:00

  • ATF2, but not ATF3, participates in the maintenance of nerve injury-induced tactile allodynia and thermal hyperalgesia.

    abstract::Transcription factors are proteins that modulate the transcriptional rate of target genes in the nucleus in response to extracellular or cytoplasmic signals. Activating transcription factors 2 (ATF2) and 3 (ATF3) respond to environmental signals and maintain cellular homeostasis. There is evidence that inflammation an...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Salinas-Abarca AB,Velazquez-Lagunas I,Franco-Enzástiga Ú,Torres-López JE,Rocha-González HI,Granados-Soto V

    更新日期:2018-01-01 00:00:00

  • PAP and NT5E inhibit nociceptive neurotransmission by rapidly hydrolyzing nucleotides to adenosine.

    abstract:BACKGROUND:Prostatic acid phosphatase (PAP) and ecto-5'-nucleotidase (NT5E, CD73) produce extracellular adenosine from the nucleotide AMP in spinal nociceptive (pain-sensing) circuits; however, it is currently unknown if these are the main ectonucleotidases that generate adenosine or how rapidly they generate adenosine...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Street SE,Walsh PL,Sowa NA,Taylor-Blake B,Guillot TS,Vihko P,Wightman RM,Zylka MJ

    更新日期:2011-10-19 00:00:00

  • Nerve injury elevates functional Cav3.2 channels in superficial spinal dorsal horn.

    abstract::Cav3 channels play an important role in modulating chronic pain. However, less is known about the functional changes of Cav3 channels in superficial spinal dorsal horn in neuropathic pain states. Here, we examined the effect of partial sciatic nerve ligation (PSNL) on either expression or electrophysiological properti...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Feng XJ,Ma LX,Jiao C,Kuang HX,Zeng F,Zhou XY,Cheng XE,Zhu MY,Zhang DY,Jiang CY,Liu T

    更新日期:2019-01-01 00:00:00

  • KCNQ channels in nociceptive cold-sensing trigeminal ganglion neurons as therapeutic targets for treating orofacial cold hyperalgesia.

    abstract:BACKGROUND:Hyperexcitability of nociceptive afferent fibers is an underlying mechanism of neuropathic pain and ion channels involved in neuronal excitability are potentially therapeutic targets. KCNQ channels, a subfamily of voltage-gated K(+) channels mediating M-currents, play a key role in neuronal excitability. It ...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Abd-Elsayed AA,Ikeda R,Jia Z,Ling J,Zuo X,Li M,Gu JG

    更新日期:2015-07-31 00:00:00

  • Peripheral inflammatory injury alters the relative abundance of Gα subunits in the dorsal horn of the spinal cord and in the rostral ventromedial medulla of male rats.

    abstract:Abstract:A diverse array of G protein-coupled receptors (GPCRs) is implicated in the modulation of nociception. The efficacy and potency of several GPCR agonists change as a consequence of peripheral inflammatory injury. Whether these changes reflect alterations in expression of the G proteins themselves is not known. ...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Wattiez AS,Walder RY,Sande CM,White SR,Hammond DL

    更新日期:2017-01-01 00:00:00

  • Involvement of neutrophils and interleukin-18 in nociception in a mouse model of muscle pain.

    abstract::Muscle pain is a common condition that relates to various pathologies. Muscle overuse induces muscle pain, and neutrophils are key players in pain production. Neutrophils also play a central role in chronic pain by secreting interleukin (IL)-18. The aim of this study was to investigate the involvement of neutrophils a...

    journal_title:Molecular pain

    pub_type: 杂志文章


    authors: Yoshida S,Hagiwara Y,Tsuchiya M,Shinoda M,Koide M,Hatakeyama H,Chaweewannakorn C,Yano T,Sogi Y,Itaya N,Sekiguchi T,Yabe Y,Sasaki K,Kanzaki M,Itoi E

    更新日期:2018-01-01 00:00:00