英國(guó)科學(xué)家新近發(fā)現(xiàn),，一個(gè)名為HCN2的基因與神經(jīng)性疼痛有關(guān),，這可能有助于開發(fā)更為有效的止痛藥,，緩解神經(jīng)性的慢性疼痛,。
劍橋大學(xué)藥理學(xué)系教授彼得·邁克諾頓等人在新一期美國(guó)《科學(xué)》雜志上報(bào)告說(shuō),，他們對(duì)小鼠進(jìn)行基因改造,，使其痛覺(jué)神經(jīng)里缺少HCN2基因,，然后對(duì)小鼠施加不同的刺激，通過(guò)觀察它們作出反應(yīng)時(shí)間,，判斷其對(duì)疼痛的感覺(jué),。
研究發(fā)現(xiàn)，這類小鼠已感受不到神經(jīng)損傷引起的慢性疼痛,，但仍能感覺(jué)到正常的急性疼痛,，包括冷、熱和壓力等導(dǎo)致的疼痛,。
邁克諾頓表示,，這項(xiàng)研究的意義在于，通過(guò)刪除HCN2基因或用藥物阻止它發(fā)揮作用,，可以在不影響急性疼痛感覺(jué)的情況下消除慢性疼痛,。這在臨床上很有價(jià)值，因?yàn)榧毙蕴弁磳?duì)身體而言是有用的警告信號(hào),，保留對(duì)它的感覺(jué)對(duì)于減輕意外損傷造成的傷害非常重要,。
依據(jù)疼痛病理機(jī)制，慢性疼痛可分為傷害性疼痛和神經(jīng)性疼痛,。后者由神經(jīng)系統(tǒng)損傷或紊亂誘發(fā),，一直是困擾醫(yī)學(xué)界的難題，而阿片類藥物治療效果不佳,。(生物谷 Bioon.com)
doi:10.1126/science.1206243
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HCN2 Ion Channels Play a Central Role in Inflammatory and Neuropathic Pain
Emery, Edward C.; Young, Gareth T.; Berrocoso, Esther M.; Chen, Lubin; McNaughton, Peter A.
The rate of action potential firing in nociceptors is a major determinant of the intensity of pain. Possible modulators ofaction potential firing include the HCN ion channels, which generate an inward current, Ih, after hyperpolarization of the membrane. We found that genetic deletion of HCN2 removed the cyclic adenosine monophosphate(cAMP)–sensitive component of Ih and abolished action potential firing caused by an elevation of cAMP in nociceptors. Mice in which HCN2 was specificallydeleted in nociceptors expressing NaV1.8 had normal pain thresholds, but inflammation did not cause hyperalgesia to heat stimuli. After a nerve lesion, these miceshowed no neuropathic pain in response to thermal or mechanical stimuli. Neuropathic pain is therefore initiated by HCN2-drivenaction potential firing in NaV1.8-expressing nociceptors.
