The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury
<p>Abstract</p> <p>Background</p> <p>Peripheral nerve injuries can trigger neuropathic pain in adults but cause little or no pain when they are sustained in infancy or early childhood. This is confirmed in rodent models where neonatal nerve injury causes no pain behavio...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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SAGE Publishing
2012-04-01
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| Series: | Molecular Pain |
| Subjects: | |
| Online Access: | http://www.molecularpain.com/content/8/1/30 |
| _version_ | 1811330070995795968 |
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| author | Vega-Avelaira David McKelvey Rebecca Hathway Gareth Fitzgerald Maria |
| author_facet | Vega-Avelaira David McKelvey Rebecca Hathway Gareth Fitzgerald Maria |
| author_sort | Vega-Avelaira David |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Peripheral nerve injuries can trigger neuropathic pain in adults but cause little or no pain when they are sustained in infancy or early childhood. This is confirmed in rodent models where neonatal nerve injury causes no pain behaviour. However, delayed pain can arise in man some considerable time after nerve damage and to examine this following early life nerve injury we have carried out a longer term follow up of rat pain behaviour into adolescence and adulthood.</p> <p>Results</p> <p>Spared nerve injury (SNI) or sham surgery was performed on 10 day old (P10) rat pups and mechanical nociceptive reflex thresholds were analysed 3, 7, 14, 21, 28, 38 and 44 days post surgery. While mechanical thresholds on the ipsilateral side are not significantly different from controls for the first 2–3 weeks post P10 surgery, after that time period, beginning at 21 days post surgery (P31), the SNI group developed following early life nerve injury significant hypersensitivity compared to the other groups. Ipsilateral mechanical nociceptive threshold was 2-fold below that of the contralateral and sham thresholds at 21 days post surgery (SNI-ipsilateral 28 (±5) g control groups 69 (±9) g, p < 0.001, 3-way ANOVA, n = 6 per group). Importantly, no effect was observed on thermal thresholds. This hypersensivity was accompanied by macrophage, microglial and astrocyte activation in the DRG and dorsal horn, but no significant change in dorsal horn p38 or JNK expression. Preemptive minocycline (daily 40 mg/kg, s.c) did not prevent the effect. Ketamine (20 mg/kg, s.c), on the other hand, produced a dose-dependent reversal of mechanical nociceptive thresholds ipsilateral to the nerve injury such that thresholds return to control levels at the highest doses of 20 mg/Kg.</p> <p>Conclusions</p> <p>We report a novel consequence of early life nerve injury whereby mechanical hypersensitivity only emerges later in life. This delayed adolescent onset in mechanical pain thresholds is accompanied by neuroimmune activation and NMDA dependent central sensitization of spinal nociceptive circuits. This delayed onset in mechanical pain sensitivity may provide clues to understand the long term effects of early injury such as late onset phantom pain and the emergence of complex adolescent chronic pain syndromes.</p> |
| first_indexed | 2024-04-13T15:55:06Z |
| format | Article |
| id | doaj.art-48ea4afd40414910bed8ecf9d30102d4 |
| institution | Directory Open Access Journal |
| issn | 1744-8069 |
| language | English |
| last_indexed | 2024-04-13T15:55:06Z |
| publishDate | 2012-04-01 |
| publisher | SAGE Publishing |
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| series | Molecular Pain |
| spelling | doaj.art-48ea4afd40414910bed8ecf9d30102d42022-12-22T02:40:43ZengSAGE PublishingMolecular Pain1744-80692012-04-01813010.1186/1744-8069-8-30The emergence of adolescent onset pain hypersensitivity following neonatal nerve injuryVega-Avelaira DavidMcKelvey RebeccaHathway GarethFitzgerald Maria<p>Abstract</p> <p>Background</p> <p>Peripheral nerve injuries can trigger neuropathic pain in adults but cause little or no pain when they are sustained in infancy or early childhood. This is confirmed in rodent models where neonatal nerve injury causes no pain behaviour. However, delayed pain can arise in man some considerable time after nerve damage and to examine this following early life nerve injury we have carried out a longer term follow up of rat pain behaviour into adolescence and adulthood.</p> <p>Results</p> <p>Spared nerve injury (SNI) or sham surgery was performed on 10 day old (P10) rat pups and mechanical nociceptive reflex thresholds were analysed 3, 7, 14, 21, 28, 38 and 44 days post surgery. While mechanical thresholds on the ipsilateral side are not significantly different from controls for the first 2–3 weeks post P10 surgery, after that time period, beginning at 21 days post surgery (P31), the SNI group developed following early life nerve injury significant hypersensitivity compared to the other groups. Ipsilateral mechanical nociceptive threshold was 2-fold below that of the contralateral and sham thresholds at 21 days post surgery (SNI-ipsilateral 28 (±5) g control groups 69 (±9) g, p < 0.001, 3-way ANOVA, n = 6 per group). Importantly, no effect was observed on thermal thresholds. This hypersensivity was accompanied by macrophage, microglial and astrocyte activation in the DRG and dorsal horn, but no significant change in dorsal horn p38 or JNK expression. Preemptive minocycline (daily 40 mg/kg, s.c) did not prevent the effect. Ketamine (20 mg/kg, s.c), on the other hand, produced a dose-dependent reversal of mechanical nociceptive thresholds ipsilateral to the nerve injury such that thresholds return to control levels at the highest doses of 20 mg/Kg.</p> <p>Conclusions</p> <p>We report a novel consequence of early life nerve injury whereby mechanical hypersensitivity only emerges later in life. This delayed adolescent onset in mechanical pain thresholds is accompanied by neuroimmune activation and NMDA dependent central sensitization of spinal nociceptive circuits. This delayed onset in mechanical pain sensitivity may provide clues to understand the long term effects of early injury such as late onset phantom pain and the emergence of complex adolescent chronic pain syndromes.</p>http://www.molecularpain.com/content/8/1/30Neuropathic painMicrogliaAstrocytesSpinal cordDorsal root gangliaNeonatal |
| spellingShingle | Vega-Avelaira David McKelvey Rebecca Hathway Gareth Fitzgerald Maria The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury Molecular Pain Neuropathic pain Microglia Astrocytes Spinal cord Dorsal root ganglia Neonatal |
| title | The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury |
| title_full | The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury |
| title_fullStr | The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury |
| title_full_unstemmed | The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury |
| title_short | The emergence of adolescent onset pain hypersensitivity following neonatal nerve injury |
| title_sort | emergence of adolescent onset pain hypersensitivity following neonatal nerve injury |
| topic | Neuropathic pain Microglia Astrocytes Spinal cord Dorsal root ganglia Neonatal |
| url | http://www.molecularpain.com/content/8/1/30 |
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