Neurotensin (NT) is an endogenous 13 amino acid neuropeptide with profound opioid-independent analgesic effects. This role
of NT is thought to be mediated by both neurotensin receptor subtype 1 (NTS1) and neurotensin receptor subtype 2 (NTS2). NT and its
receptors are widely distributed in the pain circuits in central nervous system. Thus NT might modulate pain in many structures of pain
pathway, such as spinal cord, rostroventral medulla (RVM) and periaqueductal gray (PAG). Actually either intrathecal application of NT
or direct injection of NT into RVM or PAG or intracerebroventricular injection of NT showed analgesic effects. NT exerted its antinociceptive
effects in both acute pain and chronic pain models. The analgesic effects of NT were originally found in acute pain experiments.
In the case of pathological pain, for example, formalin injection induced inflammatory pain and sciatic nerve constriction induced neuropathic
pain, NT also shows antinociceptive effects. The effects exist in somatic pain as well as visceral pain induced by noxious colorectal
distension (CRD) or writhing test. It should be noted that NT plays an important role in stress-induced antinociception (SIAN), especially
in higher intensity stress experiments. However as a neuropeptide, NT is susceptible to degradation by peptidases and cannot cross
the blood-brain barrier (BBB). Great efforts have been made to find NT analogues that are more biologically stable and could inhibit pain
by systematic administration. The present review focuses on the analgesic role and the underlying mechanisms of NT and its analogues in
pain, especially in chronic pain models.
Keywords: Neurotensin, analgesia, antinociception, stress-induced antinociception, inflammatory pain, neuropathic pain, visceral pain, analogue.
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