A novel rat forelimb model of neuropathic pain produced by partial injury of the median and ulnar nerves

Abstract

The vast majority of human peripheral nerve injuries occur in the upper limb, whereas the most animal studies have been conducted using the hindlimb models of neuropathic pain, involving damages of the sciatic or lumbar spinal nerve(s). We attempted to develop a rat forelimb model of peripheral neuropathy by partial injury of the median and ulnar nerves. The halves of each nerve were transected by microscissors at about 5mm proximal from the elbow joint and behavioral signs of neuropathic pain, such as mechanical and cold allodynia, and heat hyperalgesia, were monitored up to 126 days following nerve injury. Mechanical allodynia was assessed by measuring the forepaw withdrawal threshold to von Frey filaments, and cold allodynia was evaluated by measuring the time spent in lifting or licking the forepaw after applying acetone to it. Heat hyperalgesia was also monitored by investigating the forepaw withdrawal latencies using the Hargreaves' test. After the nerve injury, the experimental animals exhibited long-lasting clear neuropathic pain-like behaviors, such as reduced forepaw withdrawal threshold to von Frey filaments, the increased response duration of the forepaw to acetone application, and the decreased withdrawal latency to radiant heat stimulation. These behaviors were significantly alleviated by administration of gabapentin (5 or 50mg/kg, i.p.) in a dose-dependent manner. Therefore, these abnormal sensitivities are interpreted as the signs of neuropathic pain following injury of the median and ulnar nerves. Our rat forelimb model of neuropathic pain may be useful for studying human neuropathic pain and screening for valuable drug candidates.

A Single Trial of Transcutaneous Electrical Nerve Stimulation Reduces Chronic Neuropathic Pain Following Median Nerve Injury in Rats

“…Our model therefore provides a reasonable representation of upper extremity neuropathic pain. Similar to the present study, partial injury of the median and ulnar nerves caused neuropathic pain symptoms, including mechanical, thermal, and cold allodynia, that lasted 18 weeks (Yi et al 2011). In that model, pain-related behaviors appeared for 6-12 weeks, after which pain status gradually recovered and reached its pre-nerve injury value after 18 weeks.…”

“…Peripheral injuries of the upper limb increase activation of microglia and astrocytes at the C7-C8 levels of the spinal cord. These glial cells secrete inflammatory cytokines, such as tumor necrosis factor (TNF) and interleukin (IL)-6, which may also contribute to chronic neuropathic pain (Yi et al 2011). Investigation of these mechanisms was beyond the scope of the present study, but is an important area for future work.…”

“…The cervical and lumbar spinal cords, through which upper and lower extremity signals are transmitted, respectively, differ in the structure and distribution of their nerve cells. In addition, depending on the area of the lesion, peripheral nerve injury to the upper and lower limbs can cause different neuropathic pain patterns and induce diverse changes in spinal cord neurons (Dowdall et al 2005;Galtrey and Fawcett 2007;Yi et al 2011). For this reason, recent studies have suggested models of upper extremity injury.…”

<p>Brain Metabolism in Rats with Neuropathic Pain Induced by Brachial Plexus Avulsion Injury and Treated via Electroacupuncture</p>

“…42 In the behavioural assessment, MWT was used to detect mechanical allodynia, which has been frequently used in the sensation tests following brachial plexus nerve, median, and ulnar nerves, and sciatic nerve injuries in previous studies. [43][44][45][46] BPAI-induced pain in the injured forelimb subsequently caused central sensitisation and facilitation of pain sensation. 47 In the present sensory tests, the mechanical threshold of the intact forepaw was measured to quantitatively measure neuropathic pain following BPAI.…”

Evaluation of Mechanical Allodynia in an Animal Immobilization Model Using the Von Frey Method

“…33,34 The Von Frey test creates a mechanical stimulus that triggers a light and constant pressure, required to determine the withdrawal of the hind paw. For the test, the rats were placed on a perforated metallic platform (7 × 7 mm, each opening), on which was placed a transparent acrylic box that measured 8 × 8 × 18 cm, to separate the animals in different compartments.…”