Frontiers in Clinical Drug Research- Central Nervous System

Author(s): Romain-Daniel Gosselin

DOI: 10.2174/9781608057795113010005

Central Glia as Prospective Targets in Chronic Pain

Pp: 44-60 (17)

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Frontiers in Clinical Drug Research- Central Nervous System

Volume: 1

Central Glia as Prospective Targets in Chronic Pain

Author(s): Romain-Daniel Gosselin

Pp: 44-60 (17)

DOI: 10.2174/9781608057795113010005

* (Excluding Mailing and Handling)

Abstract

The pharmacology against chronic, especially neuropathic, pain is largely unsatisfactory despite its high prevalence in the population, extremely debilitating nature and associated socioeconomic burden. Molecules in the current medicinal arsenal are mostly designed to symptomatologically target peripheral actors of tissue injury or components of neuronal hyperexcitability. These medicines particularly include opiates, sodium channel blockers, modulators of excitatory or inhibitory neurotransmission and anti-inflammatory drugs. However chronic pain is not merely a peripheral or neuronal condition. Indeed, a revolutionary vision has emerged over the past decade positing that amid the profound central plasticity associated with chronic pain, molecular changes occurring in glia are pivotal. A surge of interest has therefore spread in the field ultimately leading to a flourishing wealth of data with respect to the involvement of astrocytes and microglia in pathological pain in experimental models. Nevertheless, the vital roles exerted by glial cells argue in favour of the development of well-designed regulators of glial physiology rather than full inhibitors of glial physiology. In addition, despite the extent of data released regarding glial modifications in animal models, only scarce evidence point to a similar plasticity in human. The current chapter aims to expose the promising recent developments in the quest of modulators of glial activity, particularly emphasizing the hurdles embodied by their pharmacodynamics and pharmacokinetics specificities. The credibility and bench-to-hospital potential of the few disclosed emerging glia-active compounds that are currently in the pipeline are critically discussed. A foremost attention is given to the specific case of neuropathic pain owing to the important literature available in the field, but the discussion spreads to wider perspective that includes other forms of chronic pain.


Keywords: Chronic pain, neuropathic pain, glia, astrocytes, microglia, pharmacology, MAP Kinases, antibiotics, transporters, animal models, clinical trials.

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      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Trial Access" as access_base_text, CASE j.type WHEN 111 THEN true ELSE false END as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_trail` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59827241 and j.to_ip >=59827241 )) and ((j.from_date <= 1738025109 and j.to_date >= 1738025109 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 5702) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Subscribed" as access_base_text, false as terms_popup, "S" as content_download_type, null as restricted_user_access_key, null as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_corporate` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59827241 and j.to_ip >=59827241 )) and ((j.from_date <= 1738025109 and j.to_date >= 1738025109 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 5702) union (select j.user_access_id,j.volume_id,j.user_id,j.from_ip,j.to_ip,j.type,j.track,"Token Based Access" as access_base_text, false as terms_popup, "R" as content_download_type, j.uc_id as restricted_user_access_key, "v" as restricted_user_access_type, CASE j.track WHEN 0 THEN false ELSE true END as tracksAccessByVolume,"chapter" as access_level, j.chapter_id from `user_access_chapter_token` as `j` inner join `user_access_info` as `info` on `j`.`user_access_id` = `info`.`user_access_id` where ((j.from_ip <= 59827241 and j.to_ip >=59827241 )) and ((j.from_date <= 1738025109 and j.to_date >= 1738025109 and j.perpetual= 0) or (j.from_date is null and j.to_date is null and j.perpetual= 1)) and j.chapter_id = 5702)
      590μsalphaeurekaselec_live_10_06_2022UserAccess.php#1266
      Backtrace
      • 13. app/Models/UserAccess/UserAccess.php:1266
      • 14. app/Http/Controllers/ChapterController.php:1548
      • 15. vendor/laravel/framework/src/Illuminate/Routing/Controller.php:54
      • 16. vendor/laravel/framework/src/Illuminate/Routing/ControllerDispatcher.php:43
      • 17. vendor/laravel/framework/src/Illuminate/Routing/Route.php:260
    • select b.banner_link, b.banner_name, b.banner_script, b.banner_remarks, b.banner_file_name, b.banner_placement, bd.content_type, bd.content_id from `tbl_banner` as `b` inner join `tbl_banner_detail` as `bd` on `bd`.`banner_id` = `b`.`banner_id` inner join `users` as `u` on `u`.`id` = `b`.`updated_by` where `b`.`banner_ebook` = 1 and `bd`.`content_type` = 'B' and `bd`.`content_id` = 1327 and `b`.`banner_from_date` <= 1738025109 and `b`.`banner_to_date` >= 1738025109 and `b`.`banner_status` = 'A' order by `b`.`banner_id` desc
      1.13msalphaeurekaselec_live_10_06_2022Banner.php#189
      Bindings
      • 0: 1
      • 1: B
      • 2: 1327
      • 3: 1738025109
      • 4: 1738025109
      • 5: A
      Backtrace
      • 13. app/Models/Banner.php:189
      • 14. app/Http/helpers.php:404
      • 17. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 18. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    • select count(*) as aggregate from `uc_cart_products` where cart_id='a85773bc68b4669965647c5de7fca155'
      460μsalphaeurekaselec_live_10_06_2022Cart.php#271
      Backtrace
      • 15. app/Models/Cart.php:271
      • 16. view::layouts._main_menu:13
      • 18. vendor/laravel/framework/src/Illuminate/Filesystem/Filesystem.php:124
      • 19. vendor/laravel/framework/src/Illuminate/View/Engines/PhpEngine.php:58
      • 20. vendor/laravel/framework/src/Illuminate/View/Engines/CompilerEngine.php:73
    App\Models\Keywords
    11Keywords.php#?
    App\Models\Chapter
    1Chapter.php#?
    App\Models\Ebook
    1Ebook.php#?
        _token
        fSC1uXwzpJwbofHP7bFtjJflflQfILhPM0W6FYem
        uc_cart_id
        a85773bc68b4669965647c5de7fca155
        _previous
        array:1 [ "url" => "https://beta.benthamscience.com/chapter/5702" ]
        _flash
        array:2 [ "old" => [] "new" => [] ]
        PHPDEBUGBAR_STACK_DATA
        []
        path_info
        /chapter/5702
        status_code
        200
        
        status_text
        OK
        format
        html
        content_type
        text/html; charset=UTF-8
        request_query
        []
        
        request_request
        []
        
        request_headers
        0 of 0
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        request_cookies
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        response_headers
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        ClearShow all
        Date ↕MethodURLData
        #12025-01-28 00:45:09GET/chapter/57021111913