Increased nerve growth factor after rat plantar incision contributes to guarding behavior and heat hyperalgesia

Abstract

Acutely, nerve growth factor (NGF) exerts profound effects on nociceptive transmission and produces pain and hyperalgesia. In the present study, we sought to determine the tissue levels and role of NGF after a plantar incision. A substantial increase in NGF protein expression occurred in skin 4-h, 1-day and 2-days and 5-days after incision comparing contralateral uninjured skin. Plantar incision did not change NGF levels in the tibial nerve and L4-L6 dorsal root ganglia. The therapeutic effect of a monoclonal antibody against endogenous NGF was evaluated by intraperitoneal administration of a single preoperative dose of anti-NGF. Of three different doses of anti-NGF used, the highest dose 2.8 mg/kg anti-NGF attenuated or almost abolished guarding pain scores at 4-h, 1-day (>80% decrease) and 2-days after incision. This effect is dose dependent in that lower doses (1, 0.1 mg/kg) were effective only at 1-day after incision. Anti-NGF also attenuated heat hyperalgesia at 1-day and 2-days after incision when the highest dose was used. However, treatment by anti-NGF did not affect C-fibers sensitized 1-day after incision in a glabrous skin-tibial nerve in vitro preparation. In conclusion, increased NGF was present in skin after plantar incision. NGF contributes to some incision-induced pain behaviors, guarding and heat hyperalgesia. Anti-NGF did not affect the extent of sensitization of C-fibers observed in vitro.

Antibodies to Nerve Growth Factor Reverse Established Tactile Allodynia in Rodent Models of Neuropathic Pain without Tolerance

“…In conclusion, NGF seems to be a critical mediator of all types of pain, including short-term pain (McMahon et al, 1995), surgical pain (Banik et al, 2005), inflammatory pain (Woolf et al, 1994), visceral pain (Watson et al, 2006), and, as we report here, neuropathic pain. It is noteworthy that a lack of tolerance to NGF sequestration was demonstrated over a 3-week period.…”

“…In models of neuropathic pain, such as nerve trunk or spinal nerve ligation, systemic injection of neutralizing antibodies to NGF prevents both allodynia and hyperalgesia (Ramer and Bisby, 1999;Ro et al, 1999). Likewise, an antinociceptive effect has been demonstrated to a short-term noxious stimulus (McMahon et al, 1995) in an incision model of inflammatory pain (Banik et al, 2005) and in subacute inflammatory pain (Woolf et al, 1994;McMahon et al, 1995) with no inhibition of the inflammatory process (e.g., edema). Perhaps as predicted by clinical findings (Lowe et al, 1997;Zhu et al, 1999;Okragly et al, 1999), anti-NGF treatment has been shown to prevent pain from developing in response to sarcoma growth in the bone Sevcik et al, 2005), and Watson et al (2006) reported an antinociceptive effect of an NGF-neutralizing molecule (trkAd5) in a bladder model of visceral pain.…”

Neutralization of Nerve Growth Factor Induces Plasticity of ATP-Sensitive P2X3Receptors of Nociceptive Trigeminal Ganglion Neurons

“…For testing pain responses, individual mice were placed into a plastic cage with a transparent bottom surface through which behavior was recorded with a video camera. Mice were randomly assigned to four groups (six to eight per group) and received a single intraperitoneal injection of either anti-NGF [2.5 S-NGF (Sigma), 300 ng/g body weight (Banik et al, 2005)] or saline (10 l/g) 24 h before testing nociceptive responses. On the day of testing, each animal was first placed inside the test box for a 5 min adaptation period to minimize stress.…”

Astrocytes and Chronic Pain Mechanisms—The Role of Histamine, IL-1β and NGF

“…NGF-mediated effects are central to inflammatory, surgical, visceral and neuropathic pain (1,9,25,26). In developing dorsal root ganglion neurons NGF stimulates local synthesis of cAMP-response-element-binding protein, leading to retrograde transport to the neural soma (5).…”