Pain is a way of getting our neurological attention, it exists only in our psychology but is triggered by physiological damage or changes. Peripheral pain sensation has no specialized receptor organ and initiates from free nerve endings. These endings are located throughout the skin and other tissues (muscle, bone, and connective tissue).
H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2
Substance P
Tissue damage can release a range of substances which can activate signaling pathways including: potassium, serotonin, bradykinin, histamine, prostaglandins, leukotrienes and Substance P. The free nerve endings have receptors that detect local release of prostaglandins, histamine, and substance P, all of which are associated with damage to the skin or tissues.
A recent science news article in the journal Nature discusses some recent finding in relation to research article on premature babies and whether they feel pain. This question still remains essentially unanswered. Pain recognition peripherally typically involves withdrawal reflexes from various stimuli, not relying upon any "higher processing" of the stimulus. Pain recognition centrally also relies on the cortical ability to process and identify sensory information. Qiu J. Infant pain: does it hurt? Nature. 2006 Nov 9;444(7116):143-5. "At the moment, practitioners use 'pain-coding scales' to assess the amount of pain babies might feel. Each scale consists of a set of behavioural criteria, such as crying, withdrawal and facial expressions, as well as physiological indicators, such as heart rate, blood pressure and breathing patterns."
More information on pain can be found in Neuroscience (2nd ed.) Purves, D. etal., Sunderland (MA): Sinauer Associates, Inc. (c2001): Pain | Central Regulation of Pain Perception | The Perception of Pain | The Physiological Basis of Pain Modulation | Nociceptors
Page Links: Introduction | Some Recent Findings | Pain Pathway | Substance P | Podcast | References | Terms | Glossary
Bartocci M, Bergqvist LL, Lagercrantz H, Anand KJ. Pain activates cortical areas in the preterm newborn brain. Pain. 2006 May;122(1-2):109-17. "Somatosensory cortical activation occurs bilaterally following unilateral stimulation and these changes are more pronounced in male neonates or preterm neonates at lower gestational ages."
Slater R, Cantarella A, Gallella S, Worley A, Boyd S, Meek J, Fitzgerald M. Cortical pain responses in human infants. J Neurosci. 2006 Apr 5;26(14):3662-6. "We conclude that noxious information is transmitted to the preterm infant cortex from 25 weeks, highlighting the potential for both higher-level pain processing and pain-induced plasticity in the human brain from a very early age."
Mellor DJ, Diesch TJ, Gunn AJ, Bennet L. The importance of 'awareness' for understanding fetal pain. Brain Res Brain Res Rev. 2005 Nov;49(3):455-71. "...completion of the cortical nociceptive connections just after mid-gestation is only one part of the story."
Substance P was discovered in the 1930s and sequenced in 1971 as an 11 amino acid peptide. This small peptide is released by C fibers and is associated with pain reception and is also expressed centrally (central and medial amygdaloid nucleus) where it modulates fear and anxiety related behaviour. The receptor for Substance P is one of the tachykinin (neurokinin) receptor family which also recognises other two neurokinins (A and B), neurokinin 1 (NK1) is the specific receptor for Substance P. These receptors span the cell plasma membrane in seven loops or seven transmembrane domains, which signals intracellularly through coupled G proteins.
H-Arg-Pro-Lys-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 (Mr 1347.6)
References:
Harrison S, Geppetti P. Substance p. Int J Biochem Cell Biol. 2001 Jun;33(6):555-76.
Hokfelt T, Pernow B, Wahren J. Substance P: a pioneer amongst neuropeptides. J Intern Med. 2001 Jan;249(1):27-40.
This recent Podcast in Australia on the program "All in the Mind 2006-09-30 It Hurts: The Elusive Nature of Pain" is more about postnatal perception of pain, but emphasises the nature of pain perception.
"Summary: Chronic pain. Gnawing, throbbing, aching. Like a rotten apple at the core, razor blades down the spine, barbed wire coursing through the body . Talking about it is difficult enough, but does how we think about pain actually change the nature of pain itself? Many of us still consider pain as solely biological, with major implications for the treatment we seek and receive. This week - a philosopher, a top pain psychologist and a young man who understands the intimate interplay between mind and pain better than most."
Link: All in the Mind 2006-09-30 It Hurts: The Elusive Nature of Pain
Textbook
Neuroscience (2nd ed.) Purves, D. etal., Sunderland (MA): Sinauer Associates, Inc. (c2001): Pain | Central Regulation of Pain Perception | The Perception of Pain | The Physiological Basis of Pain Modulation | Nociceptors
Mechanosensitivity in Cells and Tissues Kamkin, Andre; Kiseleva, Irina, editors Moscow: Academia Publishing House Ltd. (c2005) Mechanosensitivity of Primary Afferent Nociceptors in the Pain Pathway
Reviews
Mellor DJ, Diesch TJ, Gunn AJ, Bennet L. The importance of 'awareness' for understanding fetal pain. Brain Res Brain Res Rev. 2005 Nov;49(3):455-71.
Lee SJ, Ralston HJ, Drey EA, Partridge JC, Rosen MA. Fetal pain: a systematic multidisciplinary review of the evidence. JAMA. 2005 Aug 24;294(8):947-54.
Harrison S, Geppetti P. Substance p. Int J Biochem Cell Biol. 2001 Jun;33(6):555-76.
Hokfelt T, Pernow B, Wahren J. Substance P: a pioneer amongst neuropeptides. J Intern Med. 2001 Jan;249(1):27-40.
Vanhatalo S, van Nieuwenhuizen O. Fetal pain? Brain Dev. 2000 May;22(3):145-50.
Articles
Bartocci M, Bergqvist LL, Lagercrantz H, Anand KJ. Pain activates cortical areas in the preterm newborn brain. Pain. 2006 May;122(1-2):109-17.
Slater R, Cantarella A, Gallella S, Worley A, Boyd S, Meek J, Fitzgerald M. Cortical pain responses in human infants. J Neurosci. 2006 Apr 5;26(14):3662-6.
Search Pubmed: term = Fetal Pain | Fetal Pain Sensation | Fetal Consciousness | Neonatal Pain
A delta - myelinated (fast) conducting pain fibers associated with sharp, quick pain.
C fiber - unmyelinated (slow) conducting pain fibers associated with pressure, heat, or cold.
glutamate - neurotransmitter associated with acute pain.
nociceptors - respond to skin damage either by the drop in pH or release of histamine and bradykin.
substance P - released by C fibers associated with chronic pain. Also expressed centrally (central and medial amygdaloid nucleus) where it modulates fear and anxiety related behaviour.
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Pain has many emotional connotations, while scientifically in development this still remains a difficult research area. There is more to "pain" than simply establishing the correct neural pathways, it also relates to our "awareness of pain" which suggests a relationship to central neural processing and onsciousness. This is where the controversy lies.
Development of the neural system continues throughout our entire life, from the early trilaminar embryo, through embryonic, fetal, newborn, postnatally, at puberty and continues to be remodelled at the synaptic level through our entire life.
Please email Dr Mark Hill if you wish to make a comment about this current project.