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Abstract：
BACKGROUND: Since bone marrow receives innervation from A-delta and C-fibers and since an increase in intramedullary pressure in bone marrow may induce acute pain in orthopedic patients during surgery and chronic pain in patients with bone marrow edema, skeletal pain may partly originate from bone marrow. Intraosseous lesions, such as osteomyelitis and bone cancer, are also known to produce cutaneous hypersensitivity, which might be referred pain from bone. However, little is known about pain perception in bone marrow and referred pain induced by bone disease. Thus, we carried out an in vivo electrophysiological study and behavioral study to determine whether increased intraosseous pressure of the femur induces acute pain and whether increased intraosseous pressure induces referred pain in the corresponding receptive fields of the skin.
RESULTS: Intraosseous balloon inflation caused spontaneous pain-related behavior and mechanical hyperalgesia and allodynia in the lumbosacral region. Single neuronal activities of spinal dorsal horn neurons were extracellularly isolated, and then evoked responses to non-noxious and noxious cutaneous stimuli and intraosseous balloon inflation were recorded. Ninety-four spinal dorsal horn neurons, which had somatic receptive fields at the lower back and thigh, were obtained. Sixty-two percent of the wide-dynamic-range neurons (24/39) and 86% of the high-threshold neurons (12/14) responded to intraosseous balloon inflation, while none of the low-threshold neurons (0/41) responded to intraosseous balloon inflation. Spinally administered morphine (1 µg) abolished balloon inflation-induced spontaneous pain-related behavior and mechanical hyperalgesia in awake rats and also suppressed evoked activities of wide-dynamic-range neurons to noxious cutaneous stimulation and intraosseous balloon inflation.
CONCLUSIONS: The results suggest that mechanical stimulation to bone marrow produces nociception, concomitantly producing its referred pain in the corresponding skin fields. These mechanisms might contribute to pain caused by skeletal diseases.
RESULTS: Intraosseous balloon inflation caused spontaneous pain-related behavior and mechanical hyperalgesia and allodynia in the lumbosacral region. Single neuronal activities of spinal dorsal horn neurons were extracellularly isolated, and then evoked responses to non-noxious and noxious cutaneous stimuli and intraosseous balloon inflation were recorded. Ninety-four spinal dorsal horn neurons, which had somatic receptive fields at the lower back and thigh, were obtained. Sixty-two percent of the wide-dynamic-range neurons (24/39) and 86% of the high-threshold neurons (12/14) responded to intraosseous balloon inflation, while none of the low-threshold neurons (0/41) responded to intraosseous balloon inflation. Spinally administered morphine (1 µg) abolished balloon inflation-induced spontaneous pain-related behavior and mechanical hyperalgesia in awake rats and also suppressed evoked activities of wide-dynamic-range neurons to noxious cutaneous stimulation and intraosseous balloon inflation.
CONCLUSIONS: The results suggest that mechanical stimulation to bone marrow produces nociception, concomitantly producing its referred pain in the corresponding skin fields. These mechanisms might contribute to pain caused by skeletal diseases.
摘要：
背景：由于骨髓接受来自A-δ和C-纤维的神经支配，并且由于骨髓中髓内压力的增加可能会引起骨科患者在手术期间的急性疼痛和骨髓水肿患者的慢性疼痛，骨骼疼痛可能部分源自骨髓。骨内病变,比如骨髓炎和骨癌，还已知会产生皮肤超敏反应，这可能是骨骼疼痛。然而,对骨髓疼痛感知和骨病引起的疼痛知之甚少。因此，我们进行了一项体内电生理研究和行为研究，以确定股骨骨内压力增加是否会引起急性疼痛，以及骨内压力增加是否会引起相应皮肤感受区的相关疼痛。
结果：骨内球囊膨胀引起自发的疼痛相关行为以及腰骶部的机械性痛觉过敏和异常性疼痛。脊髓背角神经元的单个神经元活动在细胞外分离，然后记录对非伤害性和伤害性皮肤刺激的诱发反应以及骨内球囊膨胀。94个脊髓背角神经元,在下背部和大腿有躯体感受野，已获得。62％的宽动态范围神经元（24/39）和86％的高阈值神经元（12/14）对骨内球囊膨胀有反应，而没有低阈值神经元（0/41）对骨内球囊充气有反应。脊柱给药吗啡（1µg）消除了清醒大鼠中球囊膨胀引起的自发性疼痛相关行为和机械性痛觉过敏，并且还抑制了宽动态范围神经元对有害皮肤刺激和骨内球囊膨胀的诱发活动。
结论：结果表明，对骨髓的机械刺激会产生伤害感受，同时在相应的皮肤领域产生其所指的疼痛。这些机制可能导致骨骼疾病引起的疼痛。
结果：骨内球囊膨胀引起自发的疼痛相关行为以及腰骶部的机械性痛觉过敏和异常性疼痛。脊髓背角神经元的单个神经元活动在细胞外分离，然后记录对非伤害性和伤害性皮肤刺激的诱发反应以及骨内球囊膨胀。94个脊髓背角神经元,在下背部和大腿有躯体感受野，已获得。62％的宽动态范围神经元（24/39）和86％的高阈值神经元（12/14）对骨内球囊膨胀有反应，而没有低阈值神经元（0/41）对骨内球囊充气有反应。脊柱给药吗啡（1µg）消除了清醒大鼠中球囊膨胀引起的自发性疼痛相关行为和机械性痛觉过敏，并且还抑制了宽动态范围神经元对有害皮肤刺激和骨内球囊膨胀的诱发活动。
结论：结果表明，对骨髓的机械刺激会产生伤害感受，同时在相应的皮肤领域产生其所指的疼痛。这些机制可能导致骨骼疾病引起的疼痛。
