Advertisement

Changes in the Spatiotemporal Expression of Local and Referred Pain Following Repeated Intramuscular Injections of Hypertonic Saline: A Longitudinal Study

      Abstract

      Intramuscular injection of hypertonic saline produces a dull ache that is felt in the muscle belly but also often refers into distal structures. We have previously observed in 2 subjects that the pattern of pain referral alters during painful stimuli separated by a week. In this investigation, we tested the hypothesis that the intensity and area of pain in the local and referred regions exhibits plasticity when an identical noxious stimulus is delivered to the same site over sequential trials. Bolus 1 mL intramuscular injections of 5% hypertonic saline were made into the same site of the tibialis anterior (TA) muscle on the same day each week for 4 consecutive weeks. Twenty-one subjects mapped the areas of local and referred pain and rated the intensities on a visual analog scale every 30 seconds until the cessation of pain. Over 4 weeks there was a progressive reduction in the area and intensity of local pain and a reciprocal increase in the expression of referred pain. We conclude that the decrease in perceived local pain and increase in perceived referred pain reflects plastic processes occurring centrally.

      Perspective

      What happens to the intensity of pain induced by repeated noxious stimuli over time? Does it stay the same, increase or decrease? Here we show that weekly injections of hypertonic saline into the tibialis anterior cause decreases in local but increases in referred pain, suggesting central changes in processing noxious inputs.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Arendt-Nielsen L.
        • Graven-Nielsen T.
        • Svensson P.
        • Jensen T.S.
        Temporal summation in muscles and referred pain areas: an experimental human study.
        Muscle Nerve. 1997; 20: 1311-1313
        • Birbaumer N.
        • Lutzenberger W.
        • Montoya P.
        • Larbig W.
        • Unertl K.
        • Topfner S.
        • Grodd W.
        • Taub E.
        • Flor H.
        Effects of regional anesthesia on phantom limb pain are mirrored in changes in cortical reorganization.
        J Neurosci. 1997; 17: 5503-5508
        • Cook A.J.
        • Woolf C.J.
        • Wall P.D.
        • McMahon S.B.
        Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input.
        Nature. 1987; 325: 151-153
        • Feinstein B.
        • Langton J.N.
        • Jameson R.M.
        • Schiller F.
        Experiments on pain referred from deep somatic tissues.
        J Bone Joint Surg Am 36-A:981-997. 1954;
        • Flor H.
        • Elbert T.
        • Knecht S.
        • Wienbruch C.
        • Pantev C.
        • Birbaumer N.
        • Larbig W.
        • Taub E.
        Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation.
        Nature. 1995; 375: 482-484
        • Foreman R.D.
        • Blair R.W.
        • Weber N.
        Viscerosomatic convergence onto T2-T4 spinoreticular, spinoreticular-spinothalamic, and spinothalamic tract neurons in the cat.
        Exp Neurol. 1984; 85: 597-619
        • Ge H.Y.
        • Madeleine P.
        • Arendt-Nielsen L.
        Sex differences in temporal characteristics of descending inhibitory control: An evaluation using repeated bilateral experimental induction of muscle pain.
        Pain. 2004; 110: 72-78
        • Gibson W.
        • Arendt-Nielsen L.
        • Graven-Nielsen T.
        Referred pain and hyperalgesia in human tendon and muscle belly tissue.
        Pain. 2006; 120: 113-123
        • Graven-Nielsen T.
        Fundamentals of muscle pain, referred pain, and deep tissue hyperalgesia.
        Scand J Rheumatol Suppl. 2006; : 1-43
        • Graven-Nielsen T.
        • Arendt-Nielsen L.
        • Svensson P.
        • Jensen T.S.
        Experimental muscle pain: A quantitative study of local and referred pain in humans following injection of hypertonic saline.
        J Musculoskel Pain. 1997; 5: 49-69
        • Graven-Nielsen T.
        • Arendt-Nielsen L.
        • Svensson P.
        • Jensen T.S.
        Quantification of local and referred muscle pain in humans after sequential i.m. injections of hypertonic saline.
        Pain. 1997; 69: 111-117
        • Graven-Nielsen T.
        • Arendt-Nielsen L.
        • Svensson P.
        • Jensen T.S.
        Stimulus-response functions in areas with experimentally induced referred muscle pain–a psychophysical study.
        Brain Res. 1997; 744: 121-128
        • Henderson L.A.
        • Bandler R.
        • Gandevia S.C.
        • Macefield V.G.
        Distinct forebrain activity patterns during deep versus superficial pain.
        Pain. 2006; 120: 286-296
        • Hoheisel U.
        • Mense S.
        Long-term changes in discharge behaviour of cat dorsal horn neurones following noxious stimulation of deep tissues.
        Pain. 1989; 36: 239-247
        • Hoheisel U.
        • Mense S.
        • Simons D.G.
        • Yu X.M.
        Appearance of new receptive fields in rat dorsal horn neurons following noxious stimulation of skeletal muscle: A model for referral of muscle pain?.
        Neurosci Lett. 1993; 153: 9-12
        • Hylden J.L.
        • Nahin R.L.
        • Traub R.J.
        • Dubner R.
        Expansion of receptive fields of spinal lamina I projection neurons in rats with unilateral adjuvant-induced inflammation: The contribution of dorsal horn mechanisms.
        Pain. 1989; 37: 229-243
        • Kellgren J.H.
        Observations on referred pain arising from muscle.
        Clin Sci. 1938; 3: 175-190
        • Laird J.M.
        • Cervero F.
        A comparative study of the changes in receptive-field properties of multireceptive and nocireceptive rat dorsal horn neurons following noxious mechanical stimulation.
        J Neurophysiol. 1989; 62: 854-863
        • Laursen R.J.
        • Graven-Nielsen T.
        • Jensen T.S.
        • Arendt-Nielsen L.
        The effect of differential and complete nerve block on experimental muscle pain in humans.
        Muscle Nerve. 1999; 2: 1564-1570
        • Li L.
        • Ge H.
        • Yue S.
        • Arendt-Nielsen L.
        Nociceptive and non-nociceptive hypersensitivity at latent myofascial trigger points.
        Clin J Pain. 2009; 25: 132
        • Macefield V.G.
        • Gandevia S.C.
        • Henderson L.A.
        Discrete changes in cortical activation during experimentally induced referred muscle pain: A single-trial fMRI study.
        Cereb Cortex. 2007; 17: 2050-2059
        • Ren K.
        • Williams G.M.
        • Ruda M.A.
        • Dubner R.
        Inflammation and hyperalgesia in rats neonatally treated with capsaicin: Effects on two classes of nociceptive neurons in the superficial dorsal horn.
        Pain. 1994; 59: 287-300
        • Rubin T.K.
        • Gandevia S.C.
        • Henderson L.A.
        • Macefield V.G.
        Effects of intramuscular anesthesia on the expression of primary and referred pain induced by intramuscular injection of hypertonic saline.
        J Pain. 2009; 10: 829-835
        • Schulte H.
        • Graven-Nielsen T.
        • Sollevi A.
        • Jansson Y.
        • Arendt-Nielsen L.
        • Segerdahl M.
        Pharmacological modulation of experimental phasic and tonic muscle pain by morphine, alfentanil and ketamine in healthy volunteers.
        Acta Anaesthesiol Scand. 2003; 47: 1020-1030
        • Schulte H.
        • Segerdahl M.
        • Graven-Nielsen T.
        • Grass S.
        Reduction of human experimental muscle pain by alfentanil and morphine.
        Eur J Pain. 2006; 10: 733-741
        • Stohler C.S.
        • Kowalski C.J.
        Spatial and temporal summation of sensory and affective dimensions of deep somatic pain.
        Pain. 1999; 79: 165-173
        • Wolff B.B.
        • Jarvik M.E.
        Quantitative Measures of Deep Somatic Pain: Further Studies with Hypertonic Saline.
        Clin Sci. 1965; 28: 43-56
        • Wrigley P.J.
        • Press S.R.
        • Gustin S.M.
        • Macefield V.G.
        • Gandevia S.C.
        • Cousins M.J.
        • Middleton J.W.
        • Henderson L.A.
        • Siddall P.J.
        Neuropathic pain and primary somatosensory cortex reorganization following spinal cord injury.
        Pain. 2009; 141: 52-59