Carbamazepine Potentiates the Effectiveness of Morphine in a Rodent Model of Neuropathic Pain
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{"title"=>"Carbamazepine potentiates the effectiveness of morphine in a rodent model of neuropathic pain", "type"=>"journal", "authors"=>[{"first_name"=>"Michael R.", "last_name"=>"Due", "scopus_author_id"=>"55924318200"}, {"first_name"=>"Xiao Fang", "last_name"=>"Yang", "scopus_author_id"=>"55533044400"}, {"first_name"=>"Yohance M.", "last_name"=>"Allette", "scopus_author_id"=>"49661143600"}, {"first_name"=>"Aaron L.", "last_name"=>"Randolph", "scopus_author_id"=>"57196533301"}, {"first_name"=>"Matthew S.", "last_name"=>"Ripsch", "scopus_author_id"=>"8882191900"}, {"first_name"=>"Sarah M.", "last_name"=>"Wilson", "scopus_author_id"=>"57199166732"}, {"first_name"=>"Erik T.", "last_name"=>"Dustrude", "scopus_author_id"=>"55388717000"}, {"first_name"=>"Rajesh", "last_name"=>"Khanna", "scopus_author_id"=>"7202996745"}, {"first_name"=>"Fletcher A.", "last_name"=>"White", "scopus_author_id"=>"7202579001"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84907260398", "pui"=>"600033514", "doi"=>"10.1371/journal.pone.0107399", "pmid"=>"25221944", "scopus"=>"2-s2.0-84907260398", "issn"=>"19326203"}, "id"=>"47c970bd-52d7-34e6-8868-398b6fdcc361", "abstract"=>"Approximately 60% of morphine is glucuronidated to morphine-3-glucuronide (M3G) which may aggravate preexisting pain conditions. Accumulating evidence indicates that M3G signaling through neuronal Toll-like receptor 4 (TLR4) may be central to this proalgesic signaling event. These events are known to include elevated neuronal excitability, increased voltage-gated sodium (NaV) current, tactile allodynia and decreased opioid analgesic efficacy. Using an in vitro ratiometric-based calcium influx analysis of acutely dissociated small and medium-diameter neurons derived from lumbar dorsal root ganglion (DRG), we observed that M3G-sensitive neurons responded to lipopolysaccharide (LPS) and over 35% of these M3G/LPS-responsive cells exhibited sensitivity to capsaicin. In addition, M3G-exposed sensory neurons significantly increased excitatory activity and potentiated NaV current as measured by current and voltage clamp, when compared to baseline level measurements. The M3G-dependent excitability and potentiation of NaV current in these sensory neurons could be reversed by the addition of carbamazepine (CBZ), a known inhibitor of several NaV currents. We then compared the efficacy between CBZ and morphine as independent agents, to the combined treatment of both drugs simultaneously, in the tibial nerve injury (TNI) model of neuropathic pain. The potent anti-nociceptive effects of morphine (5 mg/kg, i.p.) were observed in TNI rodents at post-injury day (PID) 7-14 and absent at PID21-28, while administration of CBZ (10 mg/kg, i.p.) alone failed to produce anti-nociceptive effects at any time following TNI (PID 7-28). In contrast to either drug alone at PID28, the combination of morphine and CBZ completely attenuated tactile hyperalgesia in the rodent TNI model. The basis for the potentiation of morphine in combination with CBZ may be due to the effects of a latent upregulation of NaV1.7 in the DRG following TNI. Taken together, our observations demonstrate a potential therapeutic use of morphine and CBZ as a combinational treatment for neuropathic pain.", "link"=>"http://www.mendeley.com/research/carbamazepine-potentiates-effectiveness-morphine-rodent-model-neuropathic-pain", "reader_count"=>19, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Librarian"=>1, "Researcher"=>3, "Student > Ph. D. Student"=>2, "Student > Master"=>9, "Other"=>1, "Student > Bachelor"=>2}, "reader_count_by_subject_area"=>{"Medicine and Dentistry"=>10, "Agricultural and Biological Sciences"=>4, "Arts and Humanities"=>1, "Business, Management and Accounting"=>1, "Chemistry"=>2, "Computer Science"=>1}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>10}, "Chemistry"=>{"Chemistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>4}, "Computer Science"=>{"Computer Science"=>1}, "Business, Management and Accounting"=>{"Business, Management and Accounting"=>1}, "Arts and Humanities"=>{"Arts and Humanities"=>1}}, "reader_count_by_country"=>{"United Kingdom"=>1, "Portugal"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1676675"], "description"=>"<p>(A) Current clamp recordings were performed on small (≥30 µm) to medium (≥40 µm) dorsal root ganglion (DRG) neurons (L1-6) from naïve rats. Firing of two to four action potentials (APs) was elicited by a 1 second depolarizing current injection (ranging from 0.1 to 0.6 nA depending on the cell) every 30 seconds. Representative recordings demonstrating that application of 3 µg/mL M3G increases the number of elicited APs. Bath applied CBZ reversed the effect of M3G-increased excitability. (B) Group data showing that M3G caused a significant increase in DRG AP firing that is reversed by CBZ (*P<0.05).</p>", "links"=>[], "tags"=>["drg", "pid", "dorsal root ganglion", "lps", "rodent TNI model", "Neuropathic pain", "preexisting pain conditions", "tibial nerve injury", "cbz", "baseline level measurements", "M 3G excitability", "tlr", "morphine", "M 3G neurons", "nav", "M 3G cells", "M 3G"], "article_id"=>1170599, "categories"=>["Biological Sciences"], "users"=>["Michael R. Due", "Xiao-Fang Yang", "Yohance M. Allette", "Aaron L. Randolph", "Matthew S. Ripsch", "Sarah M. Wilson", "Erik T. Dustrude", "Rajesh Khanna", "Fletcher A. White"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107399.g002", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Morphine_3_glucuronide_M3G_increased_excitability_of_nociceptive_dorsal_root_ganglion_neurons_is_reversed_in_the_presence_of_carbamazepine_CBZ_/1170599", "title"=>"Morphine-3-glucuronide (M3G) increased excitability of nociceptive dorsal root ganglion neurons is reversed in the presence of carbamazepine (CBZ).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:09:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1676671"], "description"=>"<p>LPS-induced calcium flux in acutely dissociated small to medium diameter sensory neurons. Fura-2 loaded primary afferent neurons were stimulated with bath applications of morphine metabolite, morphine 3 glucuronide (M3G), the TLR4 agonist LPS, and capsaicin (CAP). [Ca2+]I levels were measured as ratio fluorscence of excitation at 340/380 nm over time. Four cells were assayed in this experiment and were represented by the blue, black green and red traces. The red and black traces clearly exhibited significant calcium flux after both M3G and LPS exposure while the green and blue traces exhibited only mild to moderate responses to these exogenous stimuli. All four traces exhibited robust calcium flux responses to capsaicin.</p>", "links"=>[], "tags"=>["drg", "pid", "dorsal root ganglion", "lps", "rodent TNI model", "Neuropathic pain", "preexisting pain conditions", "tibial nerve injury", "cbz", "baseline level measurements", "M 3G excitability", "tlr", "morphine", "M 3G neurons", "nav", "M 3G cells", "M 3G"], "article_id"=>1170595, "categories"=>["Biological Sciences"], "users"=>["Michael R. Due", "Xiao-Fang Yang", "Yohance M. Allette", "Aaron L. Randolph", "Matthew S. Ripsch", "Sarah M. Wilson", "Erik T. Dustrude", "Rajesh Khanna", "Fletcher A. White"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107399.g001", "stats"=>{"downloads"=>2, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Description_of_calcium_imaging_/1170595", "title"=>"Description of calcium imaging.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:09:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1676692"], "description"=>"<p>RT-PCR analysis showing the mRNA expression profile of NaV1.7 in the DRG derived from naïve animal and at different time points following TNI; post injury day (PID) 14 and PID 28 (n = 3). RT-PCR data were analyzed using the Ct method and mRNA expression levels are expressed relative to L27- ribosomal housekeeping gene. (*P<0.05; TNI gene expression vs naive threshold baseline).</p>", "links"=>[], "tags"=>["drg", "pid", "dorsal root ganglion", "lps", "rodent TNI model", "Neuropathic pain", "preexisting pain conditions", "tibial nerve injury", "cbz", "baseline level measurements", "M 3G excitability", "tlr", "morphine", "M 3G neurons", "nav", "M 3G cells", "M 3G"], "article_id"=>1170612, "categories"=>["Biological Sciences"], "users"=>["Michael R. Due", "Xiao-Fang Yang", "Yohance M. Allette", "Aaron L. Randolph", "Matthew S. Ripsch", "Sarah M. Wilson", "Erik T. Dustrude", "Rajesh Khanna", "Fletcher A. White"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107399.g006", "stats"=>{"downloads"=>1, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Tibal_Nerve_Injury_TNI_alters_the_expression_of_neuronal_transcripts_in_rat_dorsal_root_ganglion_DRG_/1170612", "title"=>"Tibal Nerve Injury (TNI) alters the expression of neuronal transcripts in rat dorsal root ganglion (DRG).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:09:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1676689"], "description"=>"<p>(A) Neither MOR or CBZ affect tactile allodynia induced by TNI. Each line represents the groups mean and SEM of 6–10 female rats. Drug group behavior at 60 minute or 120 minute vs TNI baseline (BL) behavior. (B) Effect of co-administered MOR and CBZ on tactile allodynia in the tibial nerve injury (TNI) model at post-injury day 28. The ability of MOR/CBZ to attenuate tactile allodynia induced by TNI was dose-dependent. Each line represents the groups mean and SEM of 6–10 rats. (*P<0.05; combination therapy group vs TNI baseline (BL) behavior).</p>", "links"=>[], "tags"=>["drg", "pid", "dorsal root ganglion", "lps", "rodent TNI model", "Neuropathic pain", "preexisting pain conditions", "tibial nerve injury", "cbz", "baseline level measurements", "M 3G excitability", "tlr", "morphine", "M 3G neurons", "nav", "M 3G cells", "M 3G"], "article_id"=>1170609, "categories"=>["Biological Sciences"], "users"=>["Michael R. Due", "Xiao-Fang Yang", "Yohance M. Allette", "Aaron L. Randolph", "Matthew S. Ripsch", "Sarah M. Wilson", "Erik T. Dustrude", "Rajesh Khanna", "Fletcher A. White"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107399.g005", "stats"=>{"downloads"=>0, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_The_effect_of_intraperitoneally_administered_morphine_MOR_carbamazepine_CBZ_or_combination_of_MOR_CBZ_on_tactile_allodynia_in_the_tibial_nerve_injury_TNI_model_at_post_injury_day_PID_28_/1170609", "title"=>"The effect of intraperitoneally administered morphine (MOR), carbamazepine (CBZ) or combination of MOR/CBZ on tactile allodynia in the tibial nerve injury (TNI) model at post-injury day (PID) 28.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:09:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1676683"], "description"=>"<p>(A) The ability of MOR to attenuate tactile allodynia induced by TNI in a dose-dependent fashion was limited to 5 mg/kg. Each line represents the groups mean and SEM of 6–10 female rats. Drug group behavior at 30, 60, 90, or 120 minute vs TNI baseline (BL) behavior. (B) Time-dependent effects of intraperitoneally administered morphine (MOR) on tactile allodynia in the tibial nerve injury (TNI) model at post-injury day (PID) 14, 21 and 28. The ability of MOR to attenuate tactile allodynia induced by TNI was evident in PID 14 rats but not animals at PID21 or 28. Each line represents the groups mean and SEM of 6–10 rats. Drug group behavior at 60 minute or 120 minute vs TNI baseline (BL) behavior (*P<0.05).</p>", "links"=>[], "tags"=>["drg", "pid", "dorsal root ganglion", "lps", "rodent TNI model", "Neuropathic pain", "preexisting pain conditions", "tibial nerve injury", "cbz", "baseline level measurements", "M 3G excitability", "tlr", "morphine", "M 3G neurons", "nav", "M 3G cells", "M 3G"], "article_id"=>1170607, "categories"=>["Biological Sciences"], "users"=>["Michael R. Due", "Xiao-Fang Yang", "Yohance M. Allette", "Aaron L. Randolph", "Matthew S. Ripsch", "Sarah M. Wilson", "Erik T. Dustrude", "Rajesh Khanna", "Fletcher A. White"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107399.g004", "stats"=>{"downloads"=>1, "page_views"=>17, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Dose_and_time_effects_of_intraperitoneally_administered_morphine_MOR_on_tactile_allodynia_in_the_tibial_nerve_injury_TNI_model_at_post_injury_day_7_/1170607", "title"=>"Dose- and time-effects of intraperitoneally administered morphine (MOR) on tactile allodynia in the tibial nerve injury (TNI) model at post-injury day 7.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:09:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1676679"], "description"=>"<p>A, currents were elicited by performing voltage steps from a holding potential of −80 mV, in 5 mV increments, from −70 mV to +50 mV. B, representative traces from dorsal root ganglia cells treated with either 0.1% DMSO (Vehicle), 500 ug CBZ, 3 µM M3G, or both 3 µM M3G and 500 ug CBZ. C, peak currents (pA) were normalized to cell capacitance (pF) to measure current density (pA/pF). Asterisks indicate statistically significant differences between treatment groups and vehicle group (*P<0.05, one way ANOVA with Tukey's post-hoc test). Bars represent mean ± S.E.</p>", "links"=>[], "tags"=>["drg", "pid", "dorsal root ganglion", "lps", "rodent TNI model", "Neuropathic pain", "preexisting pain conditions", "tibial nerve injury", "cbz", "baseline level measurements", "M 3G excitability", "tlr", "morphine", "M 3G neurons", "nav", "M 3G cells", "M 3G"], "article_id"=>1170603, "categories"=>["Biological Sciences"], "users"=>["Michael R. Due", "Xiao-Fang Yang", "Yohance M. Allette", "Aaron L. Randolph", "Matthew S. Ripsch", "Sarah M. Wilson", "Erik T. Dustrude", "Rajesh Khanna", "Fletcher A. White"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107399.g003", "stats"=>{"downloads"=>2, "page_views"=>19, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Morphine_3_glucuronide_M3G_potentiation_of_sodium_currents_is_blocked_by_carbamazepine_CBZ_/1170603", "title"=>"Morphine-3-glucuronide (M3G) potentiation of sodium currents is blocked by carbamazepine (CBZ).", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-15 03:09:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1676696"], "description"=>"<p>Carbamazepine Potentiates the Effectiveness of Morphine in a Rodent Model of Neuropathic Pain - Table 2 </p>", "links"=>[], "tags"=>["drg", "pid", "dorsal root ganglion", "lps", "rodent TNI model", "Neuropathic pain", "preexisting pain conditions", "tibial nerve injury", "cbz", "baseline level measurements", "M 3G excitability", "tlr", "morphine", "M 3G neurons", "nav", "M 3G cells", "M 3G"], "article_id"=>1170615, "categories"=>["Biological Sciences"], "users"=>["Michael R. Due", "Xiao-Fang Yang", "Yohance M. Allette", "Aaron L. Randolph", "Matthew S. Ripsch", "Sarah M. Wilson", "Erik T. Dustrude", "Rajesh Khanna", "Fletcher A. White"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107399.t002", "stats"=>{"downloads"=>1, "page_views"=>8, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Carbamazepine_Potentiates_the_Effectiveness_of_Morphine_in_a_Rodent_Model_of_Neuropathic_Pain_Table_2_/1170615", "title"=>"Carbamazepine Potentiates the Effectiveness of Morphine in a Rodent Model of Neuropathic Pain - Table 2", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-15 03:09:53"}
  • {"files"=>["https://ndownloader.figshare.com/files/1676694"], "description"=>"<p>Carbamazepine Potentiates the Effectiveness of Morphine in a Rodent Model of Neuropathic Pain - Table 1 </p>", "links"=>[], "tags"=>["drg", "pid", "dorsal root ganglion", "lps", "rodent TNI model", "Neuropathic pain", "preexisting pain conditions", "tibial nerve injury", "cbz", "baseline level measurements", "M 3G excitability", "tlr", "morphine", "M 3G neurons", "nav", "M 3G cells", "M 3G"], "article_id"=>1170614, "categories"=>["Biological Sciences"], "users"=>["Michael R. Due", "Xiao-Fang Yang", "Yohance M. Allette", "Aaron L. Randolph", "Matthew S. Ripsch", "Sarah M. Wilson", "Erik T. Dustrude", "Rajesh Khanna", "Fletcher A. White"], "doi"=>"https://dx.doi.org/10.1371/journal.pone.0107399.t001", "stats"=>{"downloads"=>7, "page_views"=>18, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Carbamazepine_Potentiates_the_Effectiveness_of_Morphine_in_a_Rodent_Model_of_Neuropathic_Pain_Table_1_/1170614", "title"=>"Carbamazepine Potentiates the Effectiveness of Morphine in a Rodent Model of Neuropathic Pain - Table 1", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-09-15 03:09:53"}

PMC Usage Stats | Further Information

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Relative Metric

{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences/Cell biology", "average_usage"=>[286]}, {"subject_area"=>"/Medicine and health sciences/Pathology and laboratory medicine", "average_usage"=>[287]}, {"subject_area"=>"/Medicine and health sciences/Pharmacology", "average_usage"=>[286]}]}
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