Repeated Injections of Low-Dose Nerve Growth Factor (NGF) in Healthy Humans Maintain Muscle Pain and Facilitate Ischemic Contraction–Evoked Pain

Abstract

Objective Nerve growth factor (NGF) is essential for generating and potentiating pain responses. This double-blinded crossover study assessed NGF-evoked pain in healthy humans after repeated NGF injections in the tibialis anterior (TA) muscle compared with control injections of isotonic saline. Subjects Twenty healthy subjects participated in two experimental phases; each consisted of seven sessions over 21 days. Methods At day 0, day 2, and day 4, a low-dose NGF (1 µg) was injected. Data on daily self-reported muscle pain (using a Likert scale) were collected. Data on pressure pain thresholds (PPTs), pain evoked by nonischemic and ischemic muscle contractions (using a numerical rating scale [NRS]), pressure pain detection (PDT), and pain tolerance thresholds (PTTs) to cuff algometry were recorded before day 0 and at 1, 2, 4, 7, 10, and 21 days after the first injection. Temporal summation of pain (TSP) and conditioned pain modulation (CPM) were recorded to assess central pain mechanisms. Results Likert scores remained elevated for 9 days after NGF injection (P<0.05). PPTs at the TA muscle were decreased at day 1 until day 7 after NGF injection compared with day 0 (P=0.05). In subjects presenting with NGF-induced muscle hyperalgesia, pain NRS scores evoked by nonischemic contractions were higher after NGF injection at day 4 and day 7 (P<0.04) compared with the control condition. At all time points, higher pain NRS scores were found with ischemic compared with nonischemic contractions (P<0.05). The pain NRS after ischemic contractions was elevated following prolonged NGF hyperalgesia at day 7 compared with the control condition and day 0 (P<0.04). The PDT, PTT, TSP, and CPM remained unchanged during the period of NGF-induced hyperalgesia. Conclusions Repeated low-dose NGF injections maintain muscle pain and potentiate pain evoked by ischemic contractions during prolonged NGF hyperalgesia.

Modulation of central pain mechanisms using high‐definition transcranial direct current stimulation: A double‐blind, sham‐controlled study

“…Similar findings have been shown in a study of experimental temporomandibular joint pain by Oono et al (2011), who also suggests that CPM deficiencies in pain conditions are likely more related to the duration of clinical pain than to the pain itself (Oono et al, 2011). However, pain provocation for 3 days in the present study appears to produce similar neuroplastic changes as NGFinduced pain for 21 days in terms of changes in the CPM and TSP response (Sørensen et al, 2020). The mild-to moderate pain intensity provoked in this study may also underlie the lack of CPM modulation.…”

Hypoalgesia after exercises with painful vs. non-painful muscles in healthy subjects – a randomized cross-over study

“…The results may also be influenced by the duration of pain; injection with hypertonic saline only induced shortlasting pain that was almost normalized 4 min after the injection in contrast to chronic pain states that are consistent. Other pain models e.g., delayed-onset muscle soreness [21] or nerve-growth-factor injections [22] that induce longer lasting pain should be investigated in the future in relation to EIH.…”

A new strategy against endometriosis: Oral probiotic treatments

“…Clinically, heat sensitivity is significantly lower in P1-treated mice from W4 while tactile sensitivity is decreased by P2 treatment. Nevertheless, the expression of the Nerve Growth Factor (NGF), a potent regulator of growth, maintenance, proliferation, and survival of certain target neurons [47,48] was significantly increased by P1 treatment at W12. In women with cul-de-sac/uterosacral endometriosis, NGF has been associated with deep dyspareunia and sexual pain.…”