Time course of traumatic neuroma development

Abstract

This study was designed to characterize morphologic stages during neuroma development post amputation with an eye toward developing better treatment strategies that intervene before neuromas are fully formed. Right forelimbs of 30 Sprague Dawley rats were amputated and limb stumps were collected at 3, 7, 28, 60 and 90 Days Post Amputation (DPA). Morphology of newly formed nerves and neuromas were assessed via general histology and neurofilament protein antibody staining. Analysis revealed six morphological characteristics during nerve and neuroma development; 1) normal nerve, 2) degenerating axons, 3) axonal sprouts, 4) unorganized bundles of axons, 5) unorganized axon growth into muscles, and 6) unorganized axon growth into fibrotic tissue (neuroma). At early stages (3 & 7 DPA) after amputation, normal nerves could be identified throughout the limb stump and small areas of axonal sprouts were present near the site of injury. Signs of degenerating axons were evident from 7 to 90 DPA. From day 28 on, variability of nerve characteristics with signs of unorganized axon growth into muscle and fibrotic tissue and neuroma formation became visible in multiple areas of stump tissue. These pathological features became more evident on days 60 and 90. At 90 DPA frank neuroma formation was present in all stump tissue. By following nerve regrowth and neuroma formation after amputation we were able to identify 6 separate histological stages of nerve regrowth and neuroma development. Axonal regrowth was observed as early as 3 DPA and signs of unorganized axonal growth and neuroma formation were evident by 28 DPA. Based on these observations we speculate that neuroma treatment and or prevention strategies might be more successful if targeted at the initial stages of development and not after 28 DPA.

Application of a Porcine Small Intestine Submucosa Nerve Cap for Prevention of Neuromas and Associated Pain

“…However, Oliveira et al, studied the time course of neuroma development in rodents and demonstrated that neuroma formation begins as early as 4 weeks postamputation with fully formed neuromas present by 12 weeks. 27 This is consistent with our findings of histological correlates of neuroma formation in the SC group at 12 weeks. Finally, we saw no correlation between axon swirling and optical density scores or between optical density and behavior scores.…”

“…The variability in pain response scores before the 12-week timepoint was expected since neuromas typically take at least 12 weeks to form. 27 This behavioral pain response data indicate the Nerve Cap's potential to reduce or eliminate symptomatic neuroma formation-for both the partition and spiral insert designs.…”

The Spare Parts Concept in Sarcoma Surgery: A Systematic Review of Surgical Strategies

“…In relation to the probability of occurrence and severity of neuropathic pain and phantom limb symptomatology associated with spare parts surgery techniques, it is important to keep in mind that, when the distance between two severed injured or sectioned nerves is large, axon regeneration and regrowth occurs in an unorganized pattern. If neurorrhaphy of the severed ends is not performed, about 61% of amputee patients report residual limb pain, of which 48.7% are estimated to be caused by a sensitized neuroma [33]. Therefore, the maintenance of nerves in continuity is essential.…”

Asymptomatic traumatic neuroma

“…The available methods include conservative treatment (opioids and non-opioid analgesic, antidepressants, anticonvulsants), minimally invasive procedure (cryoablation or direct injection of corticosteroid, ethanol, phenol) as well as the total excision. Various alternative methods such as acupuncture, physical therapy, neuromodulation has also been suggested [1][2][3][4].…”

“…The patient usually reports a focal pain and a tenderness to palpation. The treatment and prevention strategies arer be more successful if targeted at the initial stages of development [3].…”