Growth Hormone May Modulate Neonatal Pain

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During the neonatal period, injury may lead to altered dorsal horn neuron development.
During the neonatal period, injury may lead to altered dorsal horn neuron development.

Growth hormone may modulate pain by blocking nociceptor sensitization induced by cutaneous inflammation in neonates, according to a study published in Pain.1

"As we know, standard pharmacological therapies for pediatric pain are not optimal," Michael P. Jankowski, PhD, from Cincinnati Children's Hospital Medical Center, told Clinical Pain Advisor. "Opioids, for example, are sometimes inadequate for pain relief but regularly cause significant adverse effects. Thus, new treatment options for pain in children are of utmost importance."

During the neonatal period, injury may lead to altered dorsal horn neuron development and, eventually, hyperresponsiveness to thermal and mechanical stimuli in adulthood.1 Peripheral A-fiber sensitization may account for this process, which may be modulated by growth hormone via insulin-like growth factor (IGF) signaling.1 The role of growth hormone in pain modulation is illustrated by the finding that patients with growth hormone deficiency exhibit resting pain.1,2 In adults, antagonists to IGF receptor 1 (IGF-Rr1) mitigate hypersensitivity to mechanical and thermal stimuli during inflammation.3

Dr Jankowski, Xiaohua Liu, PhD, and colleagues from Cincinnati Children's Hospital Medical Center in Ohio investigated the role of growth hormone in behavioral hypersensitivity during cutaneous inflammation in neonatal mouse models.1

Cutaneous inflammation of the hairy hind paw skin was induced with carrageenan (3% in 0.9% NaCl) injections (n = 3-4). Growth hormone levels were significantly reduced in the target tissue 1 day post-injection (35%, %; P <.05) and, after 3 days, returned to levels observed in inflammation-naïve naive mice.1

Pretreatment with exogenous growth hormone 3 days before inducing inflammation blocked mechanical and heat hypersensitivity. Growth hormone pretreatment also prevented cutaneous afferent sensitization.1

The researchersResults from this study show found that growth hormone modulates expression of IGF-Rr1 in dorsal root ganglion neurons. In addition, blocking IGF-Rr1 upregulation during inflammation preventsed behavioral hypersensitivity, similar to the effect observed with exogenous growth hormone pretreatment.1

Summary and Clinical Applicability

Injury that occurs during the neonatal period may alter sensory neuron development and result in hypersensitivity to thermal and mechanical stimuli later on. Data suggest that growth hormone may modulate pain via IGF signaling.

"Our results suggest that growth hormone treatment could be an alternative pain management strategy for neonatal pain. We still need to work out the mechanisms by which growth hormone is acting, and we are working on that now. But the results of our study are quite exciting and may provide a new direction of research in pediatric pain," Dr Jankowski told Clinical Pain Advisor.

Limitations

The findings of this study were limited to mouse models and need to be confirmed in clinical studies.

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References

  1. Liu X, Green KJ, Ford ZK, et al. Growth hormone regulates the sensitization of developing peripheral nociceptors during cutaneous inflammation. Pain. 2017;158(2):333-346. doi: 10.1097/j.pain.0000000000000770
  2. Cimaz R, Rusconi R, Fossali E, Careddu P. Unexpected healing of cutaneous ulcers in a short child. Lancet. 2001;358(9277):211-212. doi: 10.1016/S0140-6736(01)05413-7
  3. Miura M, Sasaki M, Mizukoshi K, et al. Peripheral sensitization caused by insulin-like growth factor 1 contributes to pain hypersensitivity after tissue injury. Pain. 2011;152(4):888-895. doi: 10.1016/j.pain.2011.01.004
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