犬瘙痒和神经性疼痛

赵博

Pruritus & Neuropathic Pain in a Dog

犬瘙痒和神经性疼痛

Hélène L.M. Ruel, DMV, DéS, MSc, DACVIM (Neurology), PhD Candidate Paulo V. Steagall, DVM, MS, PhD, DACVAA Université de Montréal Quebec, Canada

翻译：刘双元

校对：赵博

History

病史

A 4-year-old, 55-lb (25-kg), neutered male Portuguese water dog was presented for a 1-year history of intractable pruritus and excessive licking of the lateral aspect of the 5th digit of the left pelvic limb。BCS was 5/9. The pruritus began concomitantly with the growth of an erythematous cutaneous mass localized between the 4th and 5th digit on the same paw, which was later diagnosed as an abscess. The patient received an injectable course of antibiotics and corticosteroids followed by 2 oral antibiotic and corticosteroid courses over a 5-month period. There was no treatment response, so surgical excision of the mass was performed.

一只4岁55 lb（25-kg)去势雄性葡萄牙水犬，因左侧第5趾外侧顽固性瘙痒过度舔舐1年就诊。BCS为5/9。瘙痒开始伴随同一只爪第4～5趾间局灶性红斑性皮肤肿块的生长，随后被诊断为脓肿，在随后在5个月内患犬口服了2个疗程的抗生素和皮质类固醇。治疗无效，故手术切除了肿块。

After the surgery, pruritus became almost continuous (10/10 using a canine pruritus severity scale ) and persisted even after the wound had healed.A second surgical procedure was performed 3 months after the first surgery to debride the wound, and the skin over the 4th and 5th digits was fused.The patient continued to exhibit compulsive licking and biting of the pelvic limb postoperatively, so the owners were instructed to use an Elizabethan collar or a sock over the affected paw to prevent self-mutilation.

手术后，瘙痒几乎持续存在（10/10，使用犬瘙痒严重程度量表），甚至在伤口愈合后仍持续存在。第1次手术后3个月又进行了第2次手术清创，缝合第4、5趾上方皮肤。患犬术后继续表现出强迫性舔舐和啃咬后肢，因此指导主人使用伊丽莎白项圈或在患爪穿上袜子防止自残。

Because pruritus persisted, radiography and ultrasonography of the distal limb were performed;no abnormalities were present. Prednisone (0.5 mg/kg PO q24h) and diphenhydramine (2.2 mg/kg PO q8h) were administered, and the degree of pruritus decreased to 3/10. The patient was referred to a dermatologist, who administered amoxicillin–clavulanic acid for treatment of suspected pyoderma. Pruritus was diminished but not resolved (2/10). Localized biting and licking in absence of an obvious local underlying cause was suggestive of a neurologic etiology, and the dog was referred to a board-certified neurologist for further diagnostic investigation.

因瘙痒持续存在，因此拍摄了远端肢体x光及超声检查，未发现异常。给予泼尼松(0.5 mg/kg PO q24h)和苯海拉明(2.2 mg/kg PO q8h)，瘙痒评分降至3/10。患犬被转至皮肤科，接受阿莫西林克拉维酸治疗疑似的脓皮病。用药后瘙痒减轻，但未消退，瘙痒评分(2/10)。在无明显局部潜在病因的情况下，局部咬和舔提示神经系统病因，遂将该犬转诊至委员会认证的神经科医生进行进一步诊断。

Physical Examination

体格检查

Physical examination was unremarkable except for a 4-cm area of alopecia over the distal and dorsolateral aspect of the left pelvic limb and compulsive licking induced by a light touch and pin prick over the sensory distribution of the tibial nerve from the tibiofemoral joint to the extremity of the limb. The patient’s responses to the light touch and pin prick were thought to represent allodynia and hyperalgesia, respectively. Neurologic examination revealed the following changes:

体格检查除左后肢远端和背外侧有4 cm的脱毛区，轻触及针扎胫感觉神经分布的胫股关节可诱发强迫性舔舐外，其余无异常。患犬对轻触和针刺的反应分别代表痛觉异常和痛觉过敏。神经系统检查结果如下：

    Stiffness of the left pelvic limb characterized by weak flexion of the stifle and short strides

    左后肢僵硬，表现为后膝关节弯曲无力和步幅变小

    The patient favored a resting position in semisternal recumbency (ie, patient lying on his chest and left pelvic limb).

    患犬更喜欢半胸骨斜卧位休息（即患犬用胸部和左后肢躺着）。

    Decreased postural reactions on the left pelvic limb as compared with the ipsilateral side, which was normal

    与正常同侧侧相比，左后肢的姿势反应减少

    Normal spinal reflexes except for an incomplete left pelvic limb withdrawal reflex as compared with the ipsilateral side, which was normal

    脊髓反射正常，但与同侧相比，左后肢回缩反射不完全，为正常

    Pain elicited (ie, the patient flinched) on palpation of the lumbosacral junction

    腰荐结合处触诊时诱发疼痛（即患犬退缩）

TREATMENT AT A GLANCE

治疗概述

    Gabapentinoids (eg, gabapentin) to block calcium currents involved in the maintenance of spinal cord central sensitization

    加巴喷丁类似物（如加巴喷丁），用于阻断参与维持脊髓中枢敏化的钙电流

    N-methyl-D-aspartate antagonists (eg, amantadine, ketamine) to prevent or treat central sensitization

    甲基-D-天冬氨酸拮抗剂（例如金刚烷胺、氯胺酮），用于预防或治疗中枢敏化

    NSAIDs to reduce peripheral inflammation and hyperalgesia

    使用非甾体抗炎药减轻外周炎症和痛觉过敏

    Transcutaneous electrical nerve stimulation used as an adjuvant therapy and as part of a multimodal analgesic approach

    经皮电神经刺激可作为辅助治疗和多模式镇痛方法的一部分

Diagnosis

诊断

CBC and serum chemistry profile results were within normal limits. CT of the left pelvic limb and lumbosacral junction revealed a mild protrusion of the intervertebral disk at the lumbosacral junction, without evidence of compression of the cauda equina or L7 spinal root. Left iliac medial and popliteal lymphadenopathy were reported.MRI of the lumbosacral junction confirmed the protrusion at L7-S1 and showed another protrusive but apparently noncompressive disk at L6-L7. Bone remodeling of the cranial facet of S1 was noted protruding into the vertebral canal. Dynamic impingement could not be ruled out.

血常规和生化检查结果均在正常范围内。CT显示左后肢及腰荐结合处椎间盘轻度突出，马尾神经及L7脊神经根没有受到压迫。左髂内和腘淋巴结肿大。MRI结果显示腰荐结合处L7-S1突出，L6-L7突出但似乎未压迫椎间盘。观察到S1头侧关节面骨结构的改变导致骨突突入椎管。无法排除动态撞击。

Concomitant allodynia and hyperalgesia localized over the area of the tibial nerve were suggestive of neuropathic pain.

同时存在的异常性疼痛和胫神经区域的痛觉过敏提示神经性疼痛。

DIAGNOSIS: INTERVERTEBRAL DISK DISEASE

诊断：椎间盘疾病

Discussion

讨论

In this case, spontaneous pruritus and excessive licking resulting in secondary abscess formation were thought to represent a sign of abnormal sensation in the affected limb (ie, dysesthesia). Neuropathic pain has no physiologic purpose and involves a lesion of the somatosensory system. Concomitant allodynia and hyperalgesia constitute a component of neuropathic pain. According to the International Association for the Study of Pain, allodynia refers to pain caused by a stimulus that does not normally provoke pain, whereas hyperalgesia corresponds to an increased sensitivity to noxious stimulation. Limb nerve entrapment and lumbosacral lesions have been described as potential causes for neuropathic pain in dogs. Diagnosis of neuropathic pain may be challenging due to the lack of validated tools for its assessment.

在本病例中，自发性瘙痒和过度舔舐导致继发脓肿的形成，代表患肢感觉异常的症状（即感觉迟钝）。神经性疼痛无生理目的，涉及身体感觉系统病变。伴随的异常性疼痛和痛觉过敏是神经性疼痛的组成部分。根据国际疼痛研究协会，异常性疼痛是指正常情况下不会引起疼痛的刺激引起的疼痛，而痛觉过敏是对伤害性刺激的敏感性增加。肢体神经压迫和腰荐病变是犬神经性疼痛的潜在原因。由于缺乏经验证的诊断评估工具，神经性疼痛的诊断可能具有挑战性。

Treatment & Long-Term Management

治疗和长期管理

The owners declined surgery and opted for medical management. The patient was successfully treated with gabapentin (10 mg/kg PO q8h), meloxicam (0.1 mg/kg PO q24h), and amantadine (3 mg/kg PO q24h). Pruritus decreased with therapy (2/10). The patient itched occasionally. Gabapentinoids (eg, gabapentin) bind to a2d-subunits of voltage-dependent calcium channels and block calcium currents involved in the maintenance of spinal cord central sensitization. Nerve injury causes increased glutamate activity. Glutamate binds to N-methylD-aspartate receptors, which contribute to spinal central sensitization.

主人拒绝手术，选择药物治疗。加巴喷丁(10 mg/kg PO q8h)、美洛昔康(0.1 mg/kg PO q24h)和金刚烷胺(3 mg/kg PO q24h)成功治疗了患犬。治疗后瘙痒减轻(2/10)。患犬偶有瘙痒。加巴喷丁类（如加巴喷丁）与电压依赖性钙离子通道的a2d亚基结合，阻断参与维持脊髓中枢敏化的钙电流。神经损伤引起谷氨酸活性增加。谷氨酸与N-甲基D-天冬氨酸受体结合，有助于脊髓中枢敏化。

Transcutaneous electrical nerve stimulation atechnique used in physiotherapy to alleviate pain via inhibition of presynaptic transmission in the dorsal horn of the spinal cord and increased release of enkephalins, endorphins, and dynorphins was used as an adjuvant therapy and as part of this patient’s multimodal analgesic approach. Transcutaneous electrical nerve stimulation has been used in humans with neuropathic pain as adjunct therapy

理疗中使用的经皮神经电刺激技术，通过抑制脊髓背角的突触前传递和增加脑啡肽、内啡肽和强啡肽的释放来缓解疼痛，被用作辅助治疗和该患犬多模式镇痛方法的一部分。经皮神经电刺激已作为辅助治疗用于神经性疼痛患犬。

Prognosis & Outcome

预后和结果

After 2 months of treatment, meloxicam was decreased to 0.1 mg/kg q48h and amantadine was decreased to approximately 1-2 mg/kg q48h for 2 weeks, when treatment with both drugs was discontinued. Gabapentin (5 mg/kg PO q8h) was used as maintenance therapy, as the dog was mostly comfortable and only occasionally exhibited shaking of the left pelvic limb. Follow up consultations every 3 months were suggested.

治疗2个月后，美洛昔康减量至0.1 mg/kg q48h，金刚烷胺减量至约1-2 mg/kg q48h，持续2周，然后中止这两种药物。使用加巴喷丁(5 mg/kg PO q8h)作为维持治疗，因为犬大多舒适，仅偶尔表现出左后肢抖动。建议每3个月进行一次复查。

Take-Home Messages

关键信息

Neuropathic pain is pain caused by a lesion or disease of the somatosensory system and should be suspected in the presence of central sensitization resulting in allodynia and hyperalgesia. Clinical signs of neuropathic pain are nonspecific and often require multidisciplinary collaboration to reach diagnosis. Surgery, primary neurologic disease, diabetes, and osteoarthritis are potential causes of neuropathic pain. The underlying mechanism of neuropathic pain is not fully understood but likely involves hyperexcitability of afferent neurons, peripheral and central sensitization, and activation of the microglia. Neuropathic pain is commonly refractory to conventional analgesia and requires a multimodal approach.

神经性疼痛是由躯体感觉系统病变或疾病引起的疼痛，存在中枢敏化导致异常性疼痛和痛觉过敏时应怀疑。神经性疼痛的临床症状是非特异性的，通常需要多学科合作才能得出诊断。手术、原发性神经系统疾病、糖尿病和骨关节炎是神经性疼痛的可能原因。神经性疼痛的潜在机制尚不完全清楚，但可能涉及传入神经元的过度兴奋、外周和中枢敏化以及小胶质细胞的激活。常规镇痛通常难以治愈神经性疼痛，需要多模式方法。

Clinical signs of neuropathic pain are nonspecific and often require multidisciplinary collaboration to reach diagnosis.

神经病理性疼痛的临床体征是非特异性的，通常需要多学科合作才能得出诊断。

References参考文献

1. Rybnícek J, Lau-Gillard PJ, Harvey R, Hill PB. Further validation of a pruritus severity scale for use in dogs. Vet Dermatol. 2009;20(2):115-122.

2. International Association for the Study of Pain. IASP terminology.

http://www.iasp-pain.org/terminology?navItemNumber=576.

Accessed August 13, 2018.

3. Mathews K, Kronen P, Lascelles D, et al. Guidelines for recognition, assessment and treatment of pain. J Small Anim Pract. 2014;55(6): E10-E68.

4. Moore SA. Managing neuropathic pain in dogs. Front Vet Sci. 2016;3(3):12.

5. Woolf CJ. Central sensitization: implications for the diagnosis and treatment of pain. Pain. 2011;152(3 Suppl):S2-S15.

6. Jin DM, Xu Y, Geng DF, Yan TB. Effect of transcutaneous electrical nerve stimulation on symptomatic diabetic peripheral neuropathy: a meta-analysis of randomized controlled trials. Diabetes Res Clin Pract. 2010;89(1):10-15.

7. Norrbrink C. Transcutaneous electrical nerve stimulation for treatment of spinal cord injury neuropathic pain. J Rehabil Res Dev.

2009;46(1):85-93.

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