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Article ; Online: Cutaneous targets for topical pain medications in patients with neuropathic pain: individual differential expression of biomarkers supports the need for personalized medicine.

Albrecht, Phillip J / Liu, Yi / Houk, George / Ruggiero, Beth / Banov, Daniel / Dockum, Marilyn / Day, A J / Rice, Frank L / Bassani, Gus

Pain reports

2024 Volume 9, Issue 2, Page(s) e1119

Abstract: Introduction: Numerous potential cutaneous targets exist for treating chronic pain with topically applied active pharmaceutical ingredients. This preliminary human skin tissue investigation was undertaken to characterize several key biomarkers in ... ...

Abstract	Introduction: Numerous potential cutaneous targets exist for treating chronic pain with topically applied active pharmaceutical ingredients. This preliminary human skin tissue investigation was undertaken to characterize several key biomarkers in keratinocytes and provide proof-of-principle data to support clinical development of topical compounded formulations for peripheral neuropathic pain syndromes, such as postherpetic neuralgia (PHN). Objectives: The study intended to identify objective biomarkers in PHN skin on a patient-by-patient personalized medicine platform. The totality of biopsy biomarker data can provide a tissue basis for directing individualized compounded topical preparations to optimize treatment efficacy. Methods: Referencing 5 of the most common actives used in topical pain relief formulations (ketamine, gabapentin, clonidine, baclofen, and lidocaine), and 3 well-established cutaneous mediators (ie, neuropeptides, cannabinoids, and vanilloids), comprehensive immunolabeling was used to quantify receptor biomarkers in skin biopsy samples taken from ipsilateral (pain) and contralateral (nonpain) dermatomes of patients with PHN. Results: Epidermal keratinocyte labeling patterns were significantly different among the cohort for each biomarker, consistent with potential mechanisms of action among keratinocytes. Importantly, the total biomarker panel indicates that the enriched PHN cohort contains distinct subgroups. Conclusion: The heterogeneity of the cohort differences may explain studies that have not shown statistical group benefit from topically administered compounded therapies. Rather, the essential need for individual tissue biomarker evaluations is evident, particularly as a means to direct a more accurately targeted topical personalized medicine approach and generate positive clinical results.
Language	English
Publishing date	2024-02-16
Publishing country	United States
Document type	Journal Article
ISSN	2471-2531
ISSN (online)	2471-2531
DOI	10.1097/PR9.0000000000001121
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Article ; Online: Fibromyalgia syndrome pathology and environmental influences on afflictions with medically unexplained symptoms.

Albrecht, Phillip J / Rice, Frank L

Reviews on environmental health

2016 Volume 31, Issue 2, Page(s) 281–294

Abstract: Fibromyalgia syndrome (FMS) is a clinical disorder predominant in females with unknown etiology and medically unexplained symptoms (MUS), similar to other afflictions, including irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), post- ... ...

Abstract	Fibromyalgia syndrome (FMS) is a clinical disorder predominant in females with unknown etiology and medically unexplained symptoms (MUS), similar to other afflictions, including irritable bowel syndrome (IBS), chronic fatigue syndrome (CFS), post-traumatic stress disorder (PTSD), Gulf War illness (GFI), and others. External environmental stimuli drive behavior and impact physiologic homeostasis (internal environment) via autonomic functioning. These environments directly impact the individual affective state (mind), which feeds back to regulate physiology (body). FMS has emerged as a complex disorder with pathologies identified among neurotransmitter and enzyme levels, immune/cytokine functionality, cortical volumes, cutaneous innervation, as well as an increased frequency among people with a history of traumatic and/or emotionally negative events, and specific personality trait profiles. Yet, quantitative physical evidence of pathology or disease etiology among FMS has been limited (as with other afflictions with MUS). Previously, our group published findings of increased peptidergic sensory innervation associated with the arterio-venous shunts (AVS) in the glabrous hand skin of FMS patients, which provides a plausible mechanism for the wide-spread FMS symptomology. This review focuses on FMS as a model affliction with MUS to discuss the implications of the recently discovered peripheral innervation alterations, explore the role of peripheral innervation to central sensitization syndromes (CSS), and examine possible estrogen-related mechanisms through which external and internal environmental factors may contribute to FMS etiology and possibly other afflictions with MUS.
MeSH term(s)	Central Nervous System/physiopathology ; Environmental Exposure/adverse effects ; Fibromyalgia/etiology ; Fibromyalgia/pathology ; Fibromyalgia/physiopathology ; Fibromyalgia/psychology ; Homeostasis ; Humans ; Life Style ; Medically Unexplained Symptoms ; Peripheral Nervous System/physiopathology ; Risk Factors ; Skin/blood supply ; Skin/innervation ; Stress, Physiological ; Stress, Psychological/complications ; Stress, Psychological/physiopathology ; Wounds and Injuries/complications ; Wounds and Injuries/physiopathology
Language	English
Publishing date	2016-06-01
Publishing country	Germany
Document type	Journal Article ; Review
ZDB-ID	184450-7
ISSN	2191-0308 ; 0048-7562 ; 0048-7554
ISSN (online)	2191-0308
ISSN	0048-7562 ; 0048-7554
DOI	10.1515/reveh-2015-0040
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Article ; Online: Cutaneous nerve fiber and peripheral Nav1.7 assessment in a large cohort of patients with postherpetic neuralgia.

Fetell, Michael / Sendel, Manon / Li, Thomas / Marinelli, Leslie / Vollert, Jan / Ruggerio, Elizaeth / Houk, George / Dockum, Marilyn / Albrecht, Phillip J / Rice, Frank L / Baron, Ralf

Pain

2023 Volume 164, Issue 11, Page(s) 2435–2446

Abstract: Abstract: The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with ... ...

Abstract	Abstract: The mechanisms of pain in postherpetic neuralgia (PHN) are still unclear, with some studies showing loss of cutaneous sensory nerve fibers that seemed to correlate with pain level. We report results of skin biopsies and correlations with baseline pain scores, mechanical hyperalgesia, and the Neuropathic Pain Symptom Inventory (NPSI) in 294 patients who participated in a clinical trial of TV-45070, a topical semiselective sodium 1.7 channel (Nav1.7) blocker. Intraepidermal nerve fibers and subepidermal Nav1.7 immunolabeled fibers were quantified in skin punch biopsies from the area of maximal PHN pain, as well as from the contralateral, homologous (mirror image) region. Across the entire study population, a 20% reduction in nerve fibers on the PHN-affected side compared with that in the contralateral side was noted; however, the reduction was much higher in older individuals, approaching 40% in those aged 70 years or older. There was a decrease in contralateral fiber counts as well, also noted in prior biopsy studies, the mechanism of which is not fully clear. Nav1.7-positive immunolabeling was present in approximately one-third of subepidermal nerve fibers and did not differ on the PHN-affected vs contralateral sides. Using cluster analysis, 2 groups could be identified, with the first cluster showing higher baseline pain, higher NPSI scores for squeezing and cold-induced pain, higher nerve fiber density, and higher Nav1.7 expression. While Nav1.7 varies from patient to patient, it does not seem to be a key pathophysiological driver of PHN pain. Individual differences in Nav1.7 expression, however, may determine the intensity and sensory aspects of pain.
MeSH term(s)	Humans ; Aged ; Neuralgia, Postherpetic/drug therapy ; Skin/innervation ; Neuralgia ; Administration, Cutaneous ; Nerve Fibers
Language	English
Publishing date	2023-06-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1097/j.pain.0000000000002950
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Article ; Online: Keratinocyte Biomarkers Distinguish Painful Diabetic Peripheral Neuropathy Patients and Correlate With Topical Lidocaine Responsiveness.

Albrecht, Phillip J / Houk, George / Ruggiero, Elizabeth / Dockum, Marilyn / Czerwinski, Margaret / Betts, Joseph / Wymer, James P / Argoff, Charles E / Rice, Frank L

Frontiers in pain research (Lausanne, Switzerland)

2021 Volume 2, Page(s) 790524

Abstract: This study investigated quantifiable measures of cutaneous innervation and algesic keratinocyte biomarkers to determine correlations with clinical measures of patient pain perception, with the intent to better discriminate between diabetic patients with ... ...

Abstract	This study investigated quantifiable measures of cutaneous innervation and algesic keratinocyte biomarkers to determine correlations with clinical measures of patient pain perception, with the intent to better discriminate between diabetic patients with painful diabetic peripheral neuropathy (PDPN) compared to patients with low-pain diabetic peripheral neuropathy (lpDPN) or healthy control subjects. A secondary objective was to determine if topical treatment with a 5% lidocaine patch resulted in correlative changes among the quantifiable biomarkers and clinical measures of pain perception, indicative of potential PDPN pain relief. This open-label proof-of-principle clinical research study consisted of a pre-treatment skin biopsy, a 4-week topical 5% lidocaine patch treatment regimen for all patients and controls, and a post-treatment skin biopsy. Clinical measures of pain and functional interference were used to monitor patient symptoms and response for correlation with quantitative skin biopsy biomarkers of innervation (PGP9.5 and CGRP), and epidermal keratinocyte biomarkers (Nav1.6, Nav1.7, CGRP). Importantly, comparable significant losses of epidermal neural innervation (intraepidermal nerve fibers; IENF) and dermal innervation were observed among PDPN and lpDPN patients compared with control subjects, indicating that innervation loss alone may not be the driver of pain in diabetic neuropathy. In pre-treatment biopsies, keratinocyte Nav1.6, Nav1.7, and CGRP immunolabeling were all significantly increased among PDPN patients compared with control subjects. Importantly, no keratinocyte biomarkers were significantly increased among the lpDPN group compared with control. In post-treatment biopsies, the keratinocyte Nav1.6, Nav1.7, and CGRP immunolabeling intensities were no longer different between control, lpDPN, or PDPN cohorts, indicating that lidocaine treatment modified the PDPN-related keratinocyte increases. Analysis of the PDPN responder population demonstrated that increased pretreatment keratinocyte biomarker immunolabeling for Nav1.6, Nav1.7, and CGRP correlated with positive outcomes to topical lidocaine treatment. Epidermal keratinocytes modulate the signaling of IENF, and several analgesic and algesic signaling systems have been identified. These results further implicate epidermal signaling mechanisms as modulators of neuropathic pain conditions, highlight a novel potential mode of action for topical treatments, and demonstrate the utility of comprehensive skin biopsy evaluation to identify novel biomarkers in clinical pain studies.
Language	English
Publishing date	2021-12-08
Publishing country	Switzerland
Document type	Journal Article
ISSN	2673-561X
ISSN (online)	2673-561X
DOI	10.3389/fpain.2021.790524
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Article ; Online: Role of small-fiber afferents in pain mechanisms with implications on diagnosis and treatment.

Albrecht, Phillip J / Rice, Frank L

Current pain and headache reports

2010 Volume 14, Issue 3, Page(s) 179–188

Abstract: Numerous mechanisms are implicated in the perception of pain. Although many anatomical, molecular, and functional components have been identified, a comprehensive and integrated theory of pain perception has yet to be firmly established that fits the ... ...

Abstract	Numerous mechanisms are implicated in the perception of pain. Although many anatomical, molecular, and functional components have been identified, a comprehensive and integrated theory of pain perception has yet to be firmly established that fits the diverse clinical experience. Acute pain involves the activation of several varieties of small primary sensory neurons, collectively termed nociceptors, which have small-caliber unmyelinated or myelinated axons (C and Adelta fibers, respectively) that innervate all body tissues. They are stimulated by noxious stimuli that activate ion channels on the endings either directly or through the release of cytokines from damaged or stressed tissues. A variety of drugs successfully treats acute pain by targeting these ion channels or cytokine interactions. Paradoxically, several chronic neuropathic pain conditions are associated with a loss of small-caliber axons and have an unpredictable and poor response to current drugs, especially at doses that do not cause severe side effects. In an attempt to further an integrated theory of pain perception, this review focuses upon the presumed role of small-caliber innervation, particularly to the epidermis and cutaneous vasculature, and the clinical manifestations, diagnosis, and treatment of pathologies of this innervation.
MeSH term(s)	Animals ; Humans ; Mechanoreceptors/cytology ; Mechanoreceptors/metabolism ; Neural Pathways/anatomy & histology ; Neurons, Afferent/cytology ; Neurons, Afferent/metabolism ; Pain/diagnosis ; Pain/physiopathology ; Skin/innervation
Language	English
Publishing date	2010-04-28
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2055062-5
ISSN	1534-3081 ; 1531-3433
ISSN (online)	1534-3081
ISSN	1531-3433
DOI	10.1007/s11916-010-0105-y
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Zs.A 5477: Show issues

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Article ; Online: A peripheral CB2 cannabinoid receptor mechanism suppresses chemotherapy-induced peripheral neuropathy: evidence from a CB2 reporter mouse.

Lin, Xiaoyan / Xu, Zhili / Carey, Lawrence / Romero, Julian / Makriyannis, Alexandros / Hillard, Cecilia J / Ruggiero, Elizabeth / Dockum, Marilyn / Houk, George / Mackie, Ken / Albrecht, Phillip J / Rice, Frank L / Hohmann, Andrea G

Pain

2021 Volume 163, Issue 5, Page(s) 834–851

Abstract: Abstract: CB2 cannabinoid receptors (CB2) are a promising therapeutic target that lacks unwanted side effects of CB1 activation. However, the cell types expressing CB2 that mediate these effects remain poorly understood. We used transgenic mice with CB2 ...

Abstract	Abstract: CB2 cannabinoid receptors (CB2) are a promising therapeutic target that lacks unwanted side effects of CB1 activation. However, the cell types expressing CB2 that mediate these effects remain poorly understood. We used transgenic mice with CB2 promoter-driven expression of enhanced green fluorescent protein (EGFP) to study cell types that express CB2 and suppress neuropathic nociception in a mouse model of chemotherapy-induced peripheral neuropathy. Structurally distinct CB2 agonists (AM1710 and LY2828360) suppressed paclitaxel-induced mechanical and cold allodynia in CB2EGFP reporter mice with established neuropathy. Antiallodynic effects of AM1710 were blocked by SR144528, a CB2 antagonist with limited CNS penetration. Intraplantar AM1710 administration suppressed paclitaxel-induced neuropathic nociception in CB2EGFP but not CB2 knockout mice, consistent with a local site of antiallodynic action. mRNA expression levels of the anti-inflammatory cytokine interleukin-10 were elevated in the lumbar spinal cord after intraplantar AM1710 injection along with the proinflammatory cytokine tumor necrosis factor alpha and chemokine monocyte chemoattractant protein-1. CB2EGFP, but not wildtype mice, exhibited anti-GFP immunoreactivity in the spleen. However, the anti-GFP signal was below the threshold for detection in the spinal cord and brain of either vehicle-treated or paclitaxel-treated CB2EGFP mice. EGFP fluorescence was coexpressed with CB2 immunolabeling in stratified patterns among epidermal keratinocytes. EGFP fluorescence was also expressed in dendritic cells in the dermis, Langerhans cells in the epidermis, and Merkel cells. Quantification of the EGFP signal revealed that Langerhans cells were dynamically increased in the epidermis after paclitaxel treatment. Our studies implicate CB2 expressed in previously unrecognized populations of skin cells as a potential target for suppressing chemotherapy-induced neuropathic nociception.
MeSH term(s)	Animals ; Antineoplastic Agents/adverse effects ; Cannabinoids/pharmacology ; Cytokines ; Hyperalgesia/chemically induced ; Hyperalgesia/drug therapy ; Mice ; Mice, Knockout ; Neuralgia/chemically induced ; Neuralgia/drug therapy ; Neuralgia/metabolism ; Paclitaxel/toxicity ; Purines ; Pyrans ; Receptor, Cannabinoid, CB1 ; Receptor, Cannabinoid, CB2/genetics
Chemical Substances	Antineoplastic Agents ; CB2 receptor agonist LY2828360 ; Cannabinoids ; Cytokines ; Purines ; Pyrans ; Receptor, Cannabinoid, CB1 ; Receptor, Cannabinoid, CB2 ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2021-12-27
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	193153-2
ISSN	1872-6623 ; 0304-3959
ISSN (online)	1872-6623
ISSN	0304-3959
DOI	10.1097/j.pain.0000000000002502
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Article ; Online: Presence of Decreased Intraepidermal Nerve Fiber Density Consistent with Small Fiber Neuropathy in Patients with Central Post-Stroke Pain.

Cavalier, Yefim / Albrecht, Phillip J / Amory, Colum / Bernardini, Gary L / Argoff, Charles E

Pain medicine (Malden, Mass.)

2016 Volume 17, Issue 8, Page(s) 1569–1571

Keywords	covid19
Language	English
Publishing date	2016-08
Publishing country	England
Document type	Letter
ZDB-ID	2015903-1
ISSN	1526-4637 ; 1526-2375
ISSN (online)	1526-4637
ISSN	1526-2375
DOI	10.1093/pm/pnw001
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Article: Human-like cutaneous neuropathologies associated with a porcine model of peripheral neuritis: A translational platform for neuropathic pain.

Rice, Frank L / Castel, David / Ruggiero, Elizabeth / Dockum, Marilyn / Houk, George / Sabbag, Itai / Albrecht, Phillip J / Meilin, Sigal

Neurobiology of pain (Cambridge, Mass.)

2018 Volume 5, Page(s) 100021

Abstract: Despite enormous investment in research and development of novel treatments, there remains a lack of predictable, effective, and safe therapeutics for human chronic neuropathic pain (NP) afflictions. NP continues to increase among the population and ... ...

Abstract	Despite enormous investment in research and development of novel treatments, there remains a lack of predictable, effective, and safe therapeutics for human chronic neuropathic pain (NP) afflictions. NP continues to increase among the population and treatments remain a major unmet public health care need. In recent years, numerous costly (time and money) failures have occurred attempting to translate successful animal pain model results, typically using rodents, to human clinical trials. These continued failures point to the essential need for better animal models of human pain conditions. To address this challenge, we have previously developed a peripheral neuritis trauma (PNT) model of chronic pain induced by a proximal sciatic nerve irritation in pigs, which have a body size, metabolism, skin structure, and cutaneous innervation more similar to humans. Here, we set out to determine the extent that the PNT model presents with cutaneous neuropathologies consistent with those associated with human chronic NP afflictions. Exactly as is performed in human skin biopsies, extensive quantitative multi-molecular immunofluorescence analyses of porcine skin biopsies were performed to assess cutaneous innervation and skin structure. ChemoMorphometric Analysis (CMA) results demonstrated a significant reduction in small caliber intraepidermal nerve fiber (IENF) innervation, altered dermal vascular innervation, and aberrant analgesic/algesic neurochemical properties among epidermal keratinocytes, which are implicated in modulating sensory innervation. These comprehensive pathologic changes very closely resemble those observed from CMA of human skin biopsies collected from NP afflictions. The results indicate that the porcine PNT model is more appropriate for translational NP research compared with commonly utilized rodent models. Because the PNT model creates cutaneous innervation and keratinocyte immunolabeling alterations consistent with human NP conditions, use of this animal model for NP testing and treatment response characteristics will likely provide more realistic results to direct successful translation to humans.
Language	English
Publishing date	2018-07-20
Publishing country	United States
Document type	Journal Article
ISSN	2452-073X
ISSN	2452-073X
DOI	10.1016/j.ynpai.2018.07.002
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Article ; Online: Efficacy of improgan, a non-opioid analgesic, in neuropathic pain.

Albrecht, Phillip J / Nalwalk, Julia W / Hough, Lindsay B

Brain research

2011 Volume 1424, Page(s) 32–37

Abstract: Improgan, a non-opioid analgesic, is known to act in the rodent brain stem to produce highly effective antinociception in several acute pain tests. However, improgan has not been studied in any models of chronic pain. To assess the efficacy of improgan ... ...

Abstract	Improgan, a non-opioid analgesic, is known to act in the rodent brain stem to produce highly effective antinociception in several acute pain tests. However, improgan has not been studied in any models of chronic pain. To assess the efficacy of improgan in an animal model of neuropathic pain, the effects of this drug were studied on mechanical allodynia following unilateral spinal nerve ligation (SNL) in rats. Intracerebroventricular (icv) improgan (40-80 μg) produced complete, reversible, dose-dependent attenuation of hind paw mechanical allodynia for up to 1h after administration, with no noticeable behavioral or motor side effects. Intracerebral (ic) microinjections of improgan (5-30 μg) into the rostral ventromedial medulla (RVM) also reversed the allodynia, showing this brain area to be an important site for improgan's action. The recently-demonstrated suppression of RVM ON-cell activity by improgan may account for the presently-observed anti-allodynic activity. The present findings suggest that brain-penetrating, improgan-like drugs developed for human use could be effective medications for the treatment of neuropathic pain.
MeSH term(s)	Analgesics, Non-Narcotic/administration & dosage ; Animals ; Axotomy ; Chronic Pain/drug therapy ; Cimetidine/administration & dosage ; Cimetidine/analogs & derivatives ; Injections, Intraventricular ; Male ; Medulla Oblongata/drug effects ; Neuralgia/drug therapy ; Rats ; Rats, Sprague-Dawley
Chemical Substances	Analgesics, Non-Narcotic ; SKF 92374 ; Cimetidine (80061L1WGD)
Language	English
Publishing date	2011-10-08
Publishing country	Netherlands
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1200-2
ISSN	1872-6240 ; 0006-8993
ISSN (online)	1872-6240
ISSN	0006-8993
DOI	10.1016/j.brainres.2011.10.002
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Article ; Online: Dorsal Root Ganglion Infiltration by Macrophages Contributes to Paclitaxel Chemotherapy-Induced Peripheral Neuropathy.

Zhang, Hongmei / Li, Yan / de Carvalho-Barbosa, Marianna / Kavelaars, Annemieke / Heijnen, Cobi J / Albrecht, Phillip J / Dougherty, Patrick M

The journal of pain : official journal of the American Pain Society

2016 Volume 17, Issue 7, Page(s) 775–786

Abstract: Unlabelled: Chemotherapy-induced peripheral neuropathy (CIPN) is a disruptive and persistent side effect of cancer treatment with paclitaxel. Recent reports showed that paclitaxel treatment results in the activation of Toll-like receptor 4 (TLR4) ... ...

Abstract	Unlabelled: Chemotherapy-induced peripheral neuropathy (CIPN) is a disruptive and persistent side effect of cancer treatment with paclitaxel. Recent reports showed that paclitaxel treatment results in the activation of Toll-like receptor 4 (TLR4) signaling and increased expression of monocyte chemoattractant protein 1 (MCP-1) in dorsal root ganglion cells. In this study, we sought to determine whether an important consequence of this signaling and also a key step in the CIPN phenotype was the recruitment and infiltration of macrophages into dorsal root ganglia (DRG). Here, we show that macrophage infiltration does occur in a time course that matches the onset of the behavioral CIPN phenotype in Sprague-Dawley rats. Moreover, depletion of macrophages by systemic administration of liposome-encapsulated clodronate (clophosome) partially reversed behavioral signs of paclitaxel-induced CIPN as well as reduced tumor necrosius factor α expression in DRG. Intrathecal injection of MCP-1 neutralizing antibodies reduced paclitaxel-induced macrophage recruitment into the DRG and also blocked the behavioral signs of CIPN. Intrathecal treatment with the TLR4 antagonist lipopolysaccharide-RS (LPS-RS) blocked mechanical hypersensitivity, reduced MCP-1 expression, and blocked the infiltration of macrophages into the DRG in paclitaxel-treated rats. The inhibition of macrophage infiltration into DRG after paclitaxel treatment with clodronate or LPS-RS prevented the loss of intraepidermal nerve fibers (IENFs) observed after paclitaxel treatment alone. These results are the first to indicate a mechanistic link such that activation of TLR4 by paclitaxel leads to increased expression of MCP-1 by DRG neurons resulting in macrophage infiltration to the DRG that express inflammatory cytokines and the combination of these events results in IENF loss and the development of behavioral signs of CIPN. Perspective: This paper shows that activation of innate immunity by paclitaxel results in a sequence of signaling events that results in the infiltration of the dorsal root ganglia by activated macrophages. Macrophages appear to drive the development of behavioral hypersensitivity and the loss of distal epidermal nerve fibers, and hence play an important role in the mechanism of paclitaxel-related neuropathy.
MeSH term(s)	Anesthetics/administration & dosage ; Animals ; Antibodies/pharmacology ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Antineoplastic Agents, Phytogenic/toxicity ; Bone Density Conservation Agents/administration & dosage ; Cell Movement/drug effects ; Chemokine CCL2/immunology ; Chemokine CCL2/metabolism ; Clodronic Acid/administration & dosage ; Disease Models, Animal ; Drug Administration Routes ; GAP-43 Protein/metabolism ; Ganglia, Spinal/pathology ; Hyperalgesia/etiology ; Isoflurane/administration & dosage ; Lipopolysaccharides/pharmacology ; Macrophages/drug effects ; Macrophages/physiology ; Male ; Paclitaxel/toxicity ; Pain Threshold/drug effects ; Peripheral Nervous System Diseases/chemically induced ; Peripheral Nervous System Diseases/drug therapy ; Peripheral Nervous System Diseases/pathology ; Rats ; Rats, Sprague-Dawley ; Spinal Cord/pathology ; Spleen/drug effects ; Spleen/pathology ; Time Factors ; Tumor Necrosis Factor-alpha/metabolism ; Ubiquitin Thiolesterase/metabolism
Chemical Substances	Anesthetics ; Antibodies ; Antigens, CD ; Antigens, Differentiation, Myelomonocytic ; Antineoplastic Agents, Phytogenic ; Bone Density Conservation Agents ; CD68 antigen, human ; Ccl2 protein, rat ; Chemokine CCL2 ; GAP-43 Protein ; Lipopolysaccharides ; Tumor Necrosis Factor-alpha ; Clodronic Acid (0813BZ6866) ; Isoflurane (CYS9AKD70P) ; UCHL1 protein, rat (EC 3.4.19.12) ; Ubiquitin Thiolesterase (EC 3.4.19.12) ; Paclitaxel (P88XT4IS4D)
Language	English
Publishing date	2016
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2018789-0
ISSN	1528-8447 ; 1526-5900
ISSN (online)	1528-8447
ISSN	1526-5900
DOI	10.1016/j.jpain.2016.02.011
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In stock of ZB MED Cologne/Königswinter

Order via subito