Repeated intramuscular injections of nerve growth factor induced progressive muscle hyperalgesia, facilitated temporal summation, and expanded pain areas

Abstract

Intramuscular injection of nerve growth factor (NGF) is known to induce deep-tissue mechanical hyperalgesia. In this study it was hypothesised that daily intramuscular injections of NGF produce a progressive manifestation of soreness, mechanical hyperalgesia, and temporal summation of pain. In a double-blind placebo-controlled design, 12 healthy subjects were injected on 3 days with NGF into the tibialis anterior muscle and with isotonic saline on the contralateral side. Assessments were performed before and after the injections on days 0, 1, and 2, and repeated on days 3, 6, and 10. The self-perceived muscle soreness was assessed on a Likert scale. Computer-controlled pressure algometry was used to assess the pressure pain thresholds (PPTs). Temporal summation of pain after repeated pressure stimulations was assessed by computer-controlled pressure algometry. The pain distribution following painful pressure stimulation was also recorded. Compared with baseline and isotonic saline, the NGF injections caused (P<0.05): (1) progressively increasing soreness scores from 3 hours after the first injection until day 2, after which it remained increased; (2) decreased PPTs at days 1 to 3; (3) facilitated temporal summation of pressure pain at days 1 to 10; and (4) enlarged pressure-induced pain area after the injection on day 1 to day 6. The daily injections of NGF produced a progressive manifestation of muscle soreness, mechanical hyperalgesia, temporal summation of pressure pain, and pressure-induced pain distribution. These data illustrate that the prolonged NGF application affects peripheral and central mechanisms and may reflect process in musculoskeletal pain conditions.

Therapeutic Potential of Inhibitors of Endocannabinoid Degradation for the Treatment of Stress-Related Hyperalgesia in an Animal Model of Chronic Pain

“…As a model of myofascial widespread pain, we used repeated intramuscular injections of nerve growth factor (NGF), which is known to be associated with fascia and muscle pain (Hoheisel et al, 2005(Hoheisel et al, , 2007Hayashi et al, 2011;Deising et al, 2012) and to induce long-lasting hyperalgesia in animals (Hoheisel et al, 2007;Mills et al, 2013) and humans (Herren-Gerber et al, 2011;Deising et al, 2012;Hayashi et al, 2013). Antibodies against NGF are currently under investigation for pain treatment in humans (Cattaneo, 2010;Pfizer, 2012).…”

Movement variability and pain: Searching for a solution

“…Pain spread into the proximal half of the forearm in 12/13 participants, similar to DOMS at the elbow (Slater et al 2003). An increase in the area of pain has also been reported following injection of NGF into the tibialis anterior muscle (Hayashi et al 2013). …”

“…Data from the present study and previous reports for other muscles provide evidence that intramuscular injection of NGF more effectively replicates these features of musculoskeletal pain conditions than injection of hypertonic saline or DOMS for several reasons. First, NGF injection induced pain that was evoked during movement for approximately one week after a single injection (Andersen et al 2008; Study 4) and two weeks after multiple injections (Hayashi et al 2013). In contrast, pain from hypertonic saline injection lasted for up to 10 minutes and DOMS-related pain was sustained for 2-3 days after exercise (Slater et al 2005).…”

Epigenetic modification of DRG neuronal gene expression subsequent to nerve injury: Etiological contribution to complex regional pain syndromes (Part I)

“…A large number of evidence indicated that NGF is expressed at high levels in injured tissues, and in involved in the facilitation of pain transmission by nociceptive neurons in the context of acute and chronic pain. Intradermal application of NGF induces long-lasting axonal and mechanical sensitization in C nociceptors that corresponds to hyperalgesia, and prolonged injections of NGF into muscle produced a progressive manifestation of muscle soreness, mechanical hyperalgesia, temporal summation of pressure pain, and pressure-induced pain distribution [91]. Furthermore, inhibition of mature NGF degradation induces a sprouting of sympathetic fibers into the upper dermis of the skin that correlated with an increase in pain-related sensitivity [92].…”