The tibial neuroma transposition (TNT) model of neuroma pain and hyperalgesia

Abstract

Peripheral nerve injury may lead to the formation of a painful neuroma. In patients, palpating the tissue overlying a neuroma evokes paraesthesias/dysaesthesias in the distribution of the injured nerve. Previous animal models of neuropathic pain have focused on the mechanical hyperalgesia and allodynia that develops at a location distant from the site of injury and not on the pain from direct stimulation of the neuroma. We describe a new animal model of neuroma pain in which the neuroma was located in a position that is accessible to mechanical testing and outside of the innervation territory of the injured nerve. This allowed testing of pain in response to mechanical stimulation of the neuroma (which we call neuroma tenderness) independent of pain due to mechanical hyperalgesia. In the tibial neuroma transposition (TNT) model, the posterior tibial nerve was ligated and transected in the foot just proximal to the plantar bifurcation. Using a subcutaneous tunnel, the end of the ligated nerve was positioned just superior to the lateral malleolus. Mechanical stimulation of the neuroma produced a profound withdrawal behavior that could be distinguished from the hyperalgesia that developed on the hind paw. The neuroma tenderness (but not the hyperalgesia) was reversed by local lidocaine injection and by proximal transection of the tibial nerve. Afferents originating from the neuroma exhibited spontaneous activity and responses to mechanical stimulation of the neuroma. The TNT model provides a useful tool to investigate the differential mechanisms underlying the neuroma tenderness and mechanical hyperalgesia associated with neuropathic pain.

Effects of tail docking and docking length on neuroanatomical changes in healed tail tips of pigs

“…Neuroma formation has been shown after nerve transection in other animal species and after removal of tails (Gross and Carr, 1990;French and Morgan, 1992), as well as other types of tissue (Breward and Gentle, 1985), including humans (Sehirlioglu et al, 2009) and rodents as part of animal-model studies using experimental nerve transection (Dorsi et al, 2008); however, previous reports have not focused on the effects of the proportion of tissue removed on neuroma formation.…”

“…In addition, neuromas have been found after healing of shoulder ulcerations in sows (DahlPedersen et al, 2013) and after experimental nerve transection in animal-model studies (Dorsi et al, 2008) in rats. After transection of an axon, growth of fine nerve processes (sprouts) from the proximal nerve end will be initiated and -if normal nerve healing is prevented by amputation or a similar process -form a neuroma, a disorderly bundle embedded in fibrous tissue (Devor and Seltzer, 1999;Burnett and Zager, 2004).…”

Alternatives to Sural Nerve Grafts in the Upper Extremity

“…Although the radial sensory nerve does not provide critical sensation to the hand, we prefer to reconstruct it because of the propensity for hyperalgesia in this region secondary to collateral sprouting [11]. Alternatively, in high radial nerve injuries, we will crush and proximally transpose the injured radial Fig.…”

Animal Models of Cancer Pain

“…43,167 Mechanical stimulation of the neuroma produces a profound withdrawal behavior in these rats. Although this model might be more representative of neuropathic pain than tumor pain, it does provide a useful tool to investigate the various mechanisms underlying the tenderness of the neuroma and mechanical hyperalgesia associated with neuropathic pain.…”

“…43,167 In the rat orofacial cancer model, squamous carcinoma cells are injected into the subperiosteal tissue of the lower gingiva. Inoculation of cancer cells induces marked mechanical allodynia and thermal hyperalgesia in the ipsilateral maxillary and mandibular nerve, and these effects are associated with increased expression of calcitonin gene related peptide, substance P, P2X 3 receptors, and TRPV1 in the trigeminal ganglia.…”