Miranda Adrian, Peles Shachar, Shaker Reza, Rudolph Colin, Sengupta Jyoti N
Division of Gastroenterology, Department of Pediatrics, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
J Physiol. 2006 May 1;572(Pt 3):775-87. doi: 10.1113/jphysiol.2006.108258.
The role ofintramuscular, low pH saline injections during the neonatal period in the development and maintenance of visceral hyperalgesia has not been systematically studied. We aimed to investigate alterations in visceral sensation and neural circuitry that result from noxious stimuli in early life. Neonatal male Sprague-Dawley rats received sterile saline injections of pH 4.0 or 7.4 in the gastrocnemius muscle starting at postnatal day 8. Injections were given unilaterally every other day for 12 days ending on postnatal day 20. A third group received needle prick only on the same shedule as the second group, while a fourth group was left naïve. At 2 months of age, rats underwent assessment of cutaneous and deep somatic sensitivity using von Frey filaments and gastrocnemius muscle pinch, respectively. A visceromotor response (VMR) to graded colorectal distension (CRD; 10-80 mmHg for 30 s with 180 s interstimulus intervals) was recorded. Extracellular single-unit recordings from the thoracolumbar spinal neurons (T13-L1) were performed in adult pH 4.0 injected and naïve controls. There was no difference in the threshold for response to mechanical stimulation of the paw in rats injected with pH 4.0 saline compared to all other groups. Conversely, rats treated with pH 4.0 saline showed a significant bilateral reduction in withdrawal threshold to muscle pinch as adults (P < 0.05). At colorectal distensions > or = 20 mmHg, an increase in the VMR was observed in the pH 4.0 injected group compared to all other groups (P < 0.05). Spinal neurons were classified as short latency abrupt (SL-A) or short latency sustained (SL-S). Spontaneous firing of SL-S (20.6 +/- 2.2 impulses s(-1)), but not SL-A neurons (5.3 +/- 0.9 impulses s(-1)) in the pH 4.0 treated rats was significantly higher than in control rats (SL-S, 2.6 +/- 0.8 impulses s(-1); SL-A, 3.1 +/- 0.7 impulses s(-1)). The response of SL-S neurons to CRD in the pH 4.0 group was significantly higher at distension pressures > or = 20 mmHg. Nociceptive somatic stimulation in neonatal rats results in chronic deep somatic and visceral hyperalgesia in adulthood. Colorectal distension-sensitive SL-S neurons are primarily sensitized to neonatal somatic stimulation.
新生儿期肌内注射低pH值盐水在内脏痛觉过敏的发生和维持中的作用尚未得到系统研究。我们旨在研究早期生活中有害刺激导致的内脏感觉和神经回路的改变。新生雄性Sprague-Dawley大鼠从出生后第8天开始在腓肠肌接受pH值为4.0或7.4的无菌盐水注射。每隔一天进行单侧注射,共12天,至出生后第20天结束。第三组与第二组在相同时间安排下仅接受针刺,而第四组不做处理。在2个月大时,分别使用von Frey细丝和捏腓肠肌评估大鼠的皮肤和深部躯体敏感性。记录对分级结肠扩张(CRD;10 - 80 mmHg,持续30秒,刺激间隔180秒)的内脏运动反应(VMR)。对成年期接受pH 4.0注射的大鼠和未处理的对照大鼠进行胸腰段脊髓神经元(T13 - L1)的细胞外单单位记录。与所有其他组相比,注射pH 4.0盐水的大鼠对爪部机械刺激的反应阈值没有差异。相反,成年后,接受pH 4.0盐水处理的大鼠对捏肌肉的撤针阈值出现显著双侧降低(P < 0.05)。在结肠扩张≥20 mmHg时,与所有其他组相比,注射pH 4.0的组中观察到VMR增加(P < 0.05)。脊髓神经元分为短潜伏期突发(SL - A)或短潜伏期持续(SL - S)。在接受pH 4.0处理的大鼠中,SL - S神经元(20.6±2.2个冲动·秒⁻¹)而非SL - A神经元(5.3±0.9个冲动·秒⁻¹)的自发放电显著高于对照大鼠(SL - S,2.6±0.8个冲动·秒⁻¹;SL - A,3.1±0.7个冲动·秒⁻¹)。在pH 4.0组中,当扩张压力≥20 mmHg时,SL - S神经元对CRD的反应显著更高。新生大鼠的伤害性躯体刺激会导致成年期慢性深部躯体和内脏痛觉过敏。对结肠扩张敏感的SL - S神经元主要对新生期躯体刺激敏感。